R. Abdel-samad, H. Zalzali, C. Rammah, J. Giraud, C. Naudin et al., MiniSOX9, a dominant-negative variant in colon cancer cells, Oncogene, vol.30, pp.2493-2503, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00615517

T. E. Adolph, M. F. Tomczak, L. Niederreiter, H. Ko, J. Böck et al., Paneth cells as a site of origin for intestinal inflammation, Nature, vol.503, pp.272-276, 2013.

M. Aguilar-medina, M. Avendaño-félix, E. Lizárraga-verdugo, M. Bermúdez, J. G. Romero-quintana et al., SOX9 Stem-Cell Factor: Clinical and Functional Relevance in Cancer, Journal of Oncology, vol.2019, pp.1-16, 2019.

A. Agus, J. Planchais, and H. Sokol, Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease, Cell Host & Microbe, vol.23, pp.716-724, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01821219

D. Akcora, D. Huynh, S. Lightowler, M. Germann, S. Robine et al., The CSF-1 receptor fashions the intestinal stem cell niche, Stem Cell Research, vol.10, pp.203-212, 2013.
URL : https://hal.archives-ouvertes.fr/hal-00789036

H. Akiyama, M. Chaboissier, J. F. Martin, A. Schedl, and B. De-crombrugghe, The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6, Genes Dev, vol.16, pp.2813-2828, 2002.

H. Akiyama, M. Chaboissier, R. R. Behringer, D. H. Rowitch, A. Schedl et al., Essential role of Sox9 in the pathway that controls formation of cardiac valves and septa, Proc. Natl. Acad. Sci. U.S.A, vol.101, pp.6502-6507, 2004.

M. Alam, T. Midtvedt, and A. Uribe, Differential cell kinetics in the ileum and colon of germfree rats, Scand. J. Gastroenterol, vol.29, pp.445-451, 1994.

S. Albac, C. Lopez-alayon, A. Schmitz, C. Enfert, M. Sautour et al., Les cellules M : une porte d'entrée pour le franchissement de la barrière intestinale par Candida albicans, Journal de Mycologie Médicale, vol.25, pp.102-103, 2015.

R. Aoki, M. Shoshkes-carmel, N. Gao, S. Shin, C. L. May et al., Foxl1-Expressing Mesenchymal Cells Constitute the Intestinal Stem Cell Niche, Cellular and Molecular Gastroenterology and Hepatology, vol.2, pp.175-188, 2016.

J. Asano, T. Sato, S. Ichinose, M. Kajita, N. Onai et al., Intrinsic Autophagy Is Required for the Maintenance of Intestinal Stem Cells and for Irradiation-Induced Intestinal Regeneration, Cell Reports, vol.20, pp.1050-1060, 2017.

T. Ayabe, D. P. Satchell, C. L. Wilson, W. C. Parks, M. E. Selsted et al., Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria, Nat. Immunol, vol.1, pp.113-118, 2000.

T. Ayabe, H. Wulff, D. Darmoul, M. D. Cahalan, K. G. Chandy et al., Modulation of mouse Paneth cell alpha-defensin secretion by mIKCa1, a Ca2+-activated, intermediate conductance potassium channel, J. Biol. Chem, vol.277, pp.3793-3800, 2002.

K. Bach-ngohou, M. M. Mahé, P. Aubert, H. Abdo, S. Boni et al., Enteric glia modulate epithelial cell proliferation and differentiation through 15-deoxy-12,14-prostaglandin J2, J. Physiol. (Lond.), vol.588, pp.2533-2544, 2010.

J. R. Bailey, P. W. Bland, J. F. Tarlton, I. Peters, M. Moorghen et al., IL-13 promotes collagen accumulation in Crohn's disease fibrosis by down-regulation of fibroblast MMP synthesis: a role for innate lymphoid cells, PLoS ONE, vol.7, p.52332, 2012.

N. Barker, Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration, Nature Reviews Molecular Cell Biology, vol.15, pp.19-33, 2014.

N. Barker and H. Clevers, Lineage Tracing in the Intestinal Epithelium, Current Protocols in Stem Cell Biology, vol.13, 2010.

N. Barker, J. H. Van-es, J. Kuipers, P. Kujala, M. Van-den-born et al., Identification of stem cells in small intestine and colon by marker gene Lgr5, Nature, vol.449, pp.1003-1007, 2007.

N. Barker, M. Van-de-wetering, and H. Clevers, The intestinal stem cell, Genes & Development, vol.22, pp.1856-1864, 2008.
URL : https://hal.archives-ouvertes.fr/pasteur-00572277

N. Barker, J. H. Van-es, V. Jaks, M. Kasper, H. Snippert et al., Very longterm self-renewal of small intestine, colon, and hair follicles from cycling Lgr5+ve stem cells, Cold Spring Harb. Symp. Quant. Biol, vol.73, pp.351-356, 2008.

N. Barker, R. A. Ridgway, J. H. Van-es, M. Van-de-wetering, H. Begthel et al., Crypt stem cells as the cells-of-origin of intestinal cancer, Nature, vol.457, pp.608-611, 2009.

F. M. Barriga, E. Montagni, M. Mana, M. Mendez-lago, X. Hernando-momblona et al., Mex3a Marks a Slowly Dividing Subpopulation of Lgr5+ Intestinal Stem Cells, Cell Stem Cell, vol.20, pp.801-816, 2017.

O. Basak, M. Van-de-born, J. Korving, J. Beumer, S. Van-der-elst et al., Mapping early fate determination in Lgr5+ crypt stem cells using a novel Ki67-RFP allele, EMBO J, vol.33, pp.2057-2068, 2014.

P. Bastide, C. Darido, J. Pannequin, R. Kist, S. Robine et al., Sox9 regulates cell proliferation and is required for Paneth cell differentiation in the intestinal epithelium, J. Cell Biol, vol.178, pp.635-648, 2007.
URL : https://hal.archives-ouvertes.fr/hal-00267010

P. Bastide, C. Darido, J. Pannequin, R. Kist, S. Robine et al., Sox9 regulates cell proliferation and is required for Paneth cell differentiation in the intestinal epithelium, The Journal of Cell Biology, vol.178, pp.635-648, 2007.
URL : https://hal.archives-ouvertes.fr/hal-00267010

E. Batlle, J. T. Henderson, H. Beghtel, M. M. Van-den-born, E. Sancho et al., Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB, Cell, vol.111, pp.251-263, 2002.

D. C. Baumgart and S. R. Carding, Inflammatory bowel disease: cause and immunobiology, Lancet, vol.369, pp.1627-1640, 2007.

J. Beumer and H. Clevers, Regulation and plasticity of intestinal stem cells during homeostasis and regeneration, Development, vol.143, pp.3639-3649, 2016.

S. Beyaz, M. D. Mana, J. Roper, D. Kedrin, A. Saadatpour et al., High-fat diet enhances stemness and tumorigenicity of intestinal progenitors, Nature, vol.531, pp.53-58, 2016.

C. Bezençon, A. Fürholz, F. Raymond, R. Mansourian, S. Métairon et al., Murine intestinal cells expressing Trpm5 are mostly brush cells and express markers of neuronal and inflammatory cells, J. Comp. Neurol, vol.509, pp.514-525, 2008.

A. Biswas, Y. Liu, L. Hao, A. Mizoguchi, N. H. Salzman et al., Induction and rescue of Nod2-dependent Th1-driven granulomatous inflammation of the ileum, Proc. Natl. Acad. Sci. U.S.A, vol.107, pp.14739-14744, 2010.

M. Biton, A. L. Haber, N. Rogel, G. Burgin, S. Beyaz et al., T Helper Cell Cytokines Modulate Intestinal Stem Cell Renewal and Differentiation, Cell, vol.175, pp.1307-1320, 2018.

. Bizzozero, Ueber die schlauchformigen Driisen des Magendarmkanals und die Beziehungen ihres Epithels zu den, Oberflachenepithel der Schleimhaut. Mikr. Anat, pp.325-375, 1892.

M. Bjerknes, Assessment of the symmetry of stem-cell mitoses, Biophysical Journal, vol.48, pp.85-91, 1985.

M. Bjerknes and H. Cheng, Clonal analysis of mouse intestinal epithelial progenitors, Gastroenterology, vol.116, pp.7-14, 1999.

M. Bjerknes and H. Cheng, Cell Lineage metastability in Gfi1-deficient mouse intestinal epithelium, Dev. Biol, vol.345, pp.49-63, 2010.

P. Blache, M. Van-de-wetering, I. Duluc, C. Domon, P. Berta et al., SOX9 is an intestine crypt transcription factor, is regulated by the Wnt pathway, and represses the CDX2 and MUC2 genes, The Journal of Cell Biology, vol.166, pp.37-47, 2004.
URL : https://hal.archives-ouvertes.fr/hal-00266987

P. Blache, M. Van-de-wetering, I. Duluc, C. Domon, P. Berta et al., SOX9 is an intestine crypt transcription factor, is regulated by the Wnt pathway, and represses the CDX2 and MUC2 genes, The Journal of Cell Biology, vol.166, pp.37-47, 2004.
URL : https://hal.archives-ouvertes.fr/hal-00266987

N. Bouladoux, T. W. Hand, S. Naik, and Y. Belkaid, Microbiote et lymphocytes T: les meilleurs ennemis, Med Sci, p.29, 2013.

K. Brandl, G. Plitas, B. Schnabl, R. P. Dematteo, and E. G. Pamer, MyD88-mediated signals induce the bactericidal lectin RegIII gamma and protect mice against intestinal Listeria monocytogenes infection, J. Exp. Med, vol.204, pp.1891-1900, 2007.

P. Bu, L. Wang, K. Chen, T. Srinivasan, P. K. Murthy et al., A miR-34a-Numb Feedforward Loop Triggered by Inflammation Regulates Asymmetric Stem Cell Division in Intestine and Colon Cancer, Cell Stem Cell, vol.18, pp.189-202, 2016.

S. J. Buczacki, H. I. Zecchini, A. M. Nicholson, R. Russell, L. Vermeulen et al., Intestinal label-retaining cells are secretory precursors expressing Lgr5, Nature, vol.495, pp.65-69, 2013.

K. Cadwell, J. Y. Liu, S. L. Brown, H. Miyoshi, J. Loh et al., A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells, Nature, vol.456, pp.259-263, 2008.

K. Cadwell, K. K. Patel, M. Komatsu, H. W. Virgin, and T. S. Stappenbeck, A common role for Atg16L1, Atg5 and Atg7 in small intestinal Paneth cells and Crohn disease, Autophagy, vol.5, pp.250-252, 2009.

K. Cadwell, K. K. Patel, N. S. Maloney, T. Liu, A. C. Ng et al., Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine, Cell, vol.141, pp.1135-1145, 2010.

A. Caicedo, V. Fritz, J. Brondello, M. Ayala, I. Dennemont et al., MitoCeption as a new tool to assess the effects of mesenchymal stem/stromal cell mitochondria on cancer cell metabolism and function, p.9073, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01834600

A. B. Cairnie, L. F. Lamerton, and G. G. Steel, Cell proliferation studies in the intestinal epithelium of the rat. I. Determination of the kinetic parameters, Exp. Cell Res, vol.39, pp.528-538, 1965.

F. Campeotto, A. Waligora-dupriet, F. Doucet-populaire, N. Kalach, C. Dupont et al., , 2007.

, Gastroenterol. Clin. Biol, vol.31, pp.533-542

K. S. Carmon, X. Gong, Q. Lin, A. Thomas, and Q. Liu, R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/beta-catenin signaling, Proc. Natl. Acad. Sci. U.S.A, vol.108, pp.11452-11457, 2011.

E. Carrasco-garcia, L. Lopez, P. Aldaz, S. Arevalo, J. Aldaregia et al., SOX9-regulated cell plasticity in colorectal metastasis is attenuated by rapamycin, Scientific Reports, vol.6, p.32350, 2016.

A. J. Carulli, T. M. Keeley, E. S. Demitrack, J. Chung, I. Maillard et al., Notch receptor regulation of intestinal stem cell homeostasis and crypt regeneration, Developmental Biology, vol.402, pp.98-108, 2015.

R. Caruso, M. Sarra, C. Stolfi, A. Rizzo, D. Fina et al., Interleukin-25 inhibits interleukin-12 production and Th1 cell-driven inflammation in the gut, Gastroenterology, vol.136, pp.2270-2279, 2009.

A. Cederlund, G. H. Gudmundsson, A. , and B. , Antimicrobial peptides important in innate immunity, FEBS J, vol.278, pp.3942-3951, 2011.

K. L. Cerveny, Y. Tamura, Z. Zhang, R. E. Jensen, and H. Sesaki, Regulation of mitochondrial fusion and division, Trends Cell Biol, vol.17, pp.563-569, 2007.

P. V. Chang, L. Hao, S. Offermanns, and R. Medzhitov, The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition, Proc. Natl. Acad. Sci. U.S.A, vol.111, pp.2247-2252, 2014.

H. Cheng, C. P. Leblond, (. The, . Of-g, A. Trigelydes et al., Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine I. Columnar cell, American Journal of Anatomy, vol.141, pp.461-479, 1974.

H. Chu, M. Pazgier, G. Jung, S. Nuccio, P. A. Castillo et al., Human ?-defensin 6 promotes mucosal innate immunity through self-assembled peptide nanonets, Science, vol.337, pp.477-481, 2012.

S. Chwalinski, C. S. Potten, and G. Evans, Double labelling with bromodeoxyuridine and [3H]-thymidine of proliferative cells in small intestinal epithelium in steady state and after irradiation, Cell Tissue Kinet, vol.21, pp.317-329, 1988.

M. A. Ciorba, T. E. Riehl, M. S. Rao, C. Moon, X. Ee et al., Lactobacillus probiotic protects intestinal epithelium from radiation injury in a TLR-2/cyclo-oxygenase-2-dependent manner, Gut, vol.61, pp.829-838, 2012.

H. Clevers, The Intestinal Crypt, A Prototype Stem Cell Compartment, Cell, vol.154, pp.274-284, 2013.

H. Clevers and E. Batlle, SnapShot: the intestinal crypt, Cell, vol.152, pp.1198-1198, 2013.

S. Colnot, M. Niwa-kawakita, G. Hamard, C. Godard, S. Le-plenier et al., Colorectal cancers in a new mouse model of familial adenomatous polyposis: influence of genetic and environmental modifiers, Lab. Invest, vol.84, pp.1619-1630, 2004.

D. M. Cornforth and K. R. Foster, Competition sensing: the social side of bacterial stress responses, Nat. Rev. Microbiol, vol.11, pp.285-293, 2013.

J. F. Cryan and T. G. Dinan, Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour, Nature Reviews Neuroscience, vol.13, pp.701-712, 2012.

S. Date and T. Sato, Mini-Gut Organoids: Reconstitution of the Stem Cell Niche, Annual Review of Cell and Developmental Biology, vol.31, pp.269-289, 2015.

R. J. Davies, R. Miller, C. , and N. , Colorectal cancer screening: prospects for molecular stool analysis, Nature Reviews Cancer, vol.5, pp.199-209, 2005.

H. Davis, S. Irshad, M. Bansal, H. Rafferty, T. Boitsova et al., Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche, Nat. Med, vol.21, pp.62-70, 2015.

L. De-orci and P. , In Freeze-Etch Histology. A Comparison between Thin Sections and Freeze-Etch Replicas, 1975.

B. Degirmenci, T. Valenta, S. Dimitrieva, G. Hausmann, and K. Basler, GLI1-expressing mesenchymal cells form the essential Wnt-secreting niche for colon stem cells, Nature, vol.558, p.449, 2018.

M. A. Diamanti, J. Gupta, M. Bennecke, T. De-oliveira, M. Ramakrishnan et al., IKK? controls ATG16L1 degradation to prevent ER stress during inflammation, J. Exp. Med, vol.214, pp.423-437, 2017.

W. A. Van-dop, A. Uhmann, M. Wijgerde, E. Sleddens-linkels, J. Heijmans et al., Depletion of the colonic epithelial precursor cell compartment upon conditional activation of the hedgehog pathway, Gastroenterology, vol.136, pp.1-7, 2009.

G. W. Dorn, Mitochondrial dynamism and heart disease: changing shape and shaping change, EMBO Molecular Medicine, vol.7, pp.865-877, 2015.

J. Drost, R. H. Van-jaarsveld, B. Ponsioen, C. Zimberlin, R. Van-boxtel et al., Sequential cancer mutations in cultured human intestinal stem cells, Nature, vol.521, pp.43-47, 2015.

S. Dupasquier, R. Abdel-samad, R. I. Glazer, P. Bastide, P. Jay et al., A new mechanism of SOX9 action to regulate PKC expression in the intestine epithelium, Journal of Cell Science, vol.122, pp.2191-2196, 2009.
URL : https://hal.archives-ouvertes.fr/hal-02459514

A. Durand, B. Donahue, G. Peignon, F. Letourneur, N. Cagnard et al., Functional intestinal stem cells after Paneth cell ablation induced by the loss of transcription factor Math1 (Atoh1), Proc. Natl. Acad. Sci. U.S.A, vol.109, pp.8965-8970, 2012.

J. H. Es, . Van, A. Haegebarth, P. Kujala, S. Itzkovitz et al., A Critical Role for the Wnt Effector Tcf4 in Adult Intestinal Homeostatic Self-Renewal, Molecular and Cellular Biology, vol.32, pp.1918-1927, 2012.

J. H. Van-es, P. Jay, A. Gregorieff, M. E. Van-gijn, S. Jonkheer et al., Wnt signalling induces maturation of Paneth cells in intestinal crypts, Nat. Cell Biol, vol.7, pp.381-386, 2005.

J. H. Van-es, M. E. Van-gijn, O. Riccio, M. Van-den-born, M. Vooijs et al., Notch/?-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells, Nature, vol.435, pp.959-963, 2005.

J. H. Van-es, T. Sato, M. Van-de-wetering, A. Lyubimova, A. N. Yee-nee et al., Dll1+ secretory progenitor cells revert to stem cells upon crypt damage, Nature Cell Biology, vol.14, pp.1099-1104, 2012.

A. M. Faria, B. S. Reis, and D. Mucida, Tissue adaptation: Implications for gut immunity and tolerance, The Journal of Experimental Medicine, vol.214, pp.1211-1226, 2017.

H. F. Farin, J. H. Van-es, and H. Clevers, Redundant sources of Wnt regulate intestinal stem cells and promote formation of Paneth cells, Gastroenterology, vol.143, pp.1518-1529, 2012.

H. F. Farin, W. R. Karthaus, P. Kujala, M. Rakhshandehroo, G. Schwank et al., Paneth cell extrusion and release of antimicrobial products is directly controlled by immune cell-derived IFN-?, J. Exp. Med, vol.211, pp.1393-1405, 2014.

J. A. Ferreyra, K. J. Wu, A. J. Hryckowian, D. M. Bouley, B. C. Weimer et al., Gut microbiota-produced succinate promotes C. difficile infection after antibiotic treatment or motility disturbance, Cell Host Microbe, vol.16, pp.770-777, 2014.

L. G. Van-der-flier and H. Clevers, Stem Cells, Self-Renewal, and Differentiation in the Intestinal Epithelium, Annual Review of Physiology, vol.71, pp.241-260, 2009.

L. G. Van-der-flier, M. E. Van-gijn, P. Hatzis, P. Kujala, A. Haegebarth et al., Transcription factor achaete scute-like 2 controls intestinal stem cell fate, Cell, vol.136, pp.903-912, 2009.

R. P. Fordham, S. Yui, N. R. Hannan, C. Soendergaard, A. Madgwick et al., Transplantation of expanded fetal intestinal progenitors contributes to colon regeneration after injury, Cell Stem Cell, vol.13, pp.734-744, 2013.

E. J. Formeister, A. L. Sionas, D. K. Lorance, C. L. Barkley, G. H. Lee et al., Distinct SOX9 levels differentially mark stem/progenitor populations and enteroendocrine cells of the small intestine epithelium, American Journal of Physiology-Gastrointestinal and Liver Physiology, vol.296, pp.1108-1118, 2009.

J. W. Foster, M. A. Dominguez-steglich, S. Guioli, C. Kwok, P. A. Weller et al., Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene, Nature, vol.372, pp.525-530, 1994.

S. Fre, M. Huyghe, P. Mourikis, S. Robine, D. Louvard et al., Notch signals control the fate of immature progenitor cells in the intestine, Nature, vol.435, pp.964-968, 2005.

Y. Furusawa, Y. Obata, S. Fukuda, T. A. Endo, G. Nakato et al., Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells, Nature, vol.504, pp.446-450, 2013.

K. Furuyama, Y. Kawaguchi, H. Akiyama, M. Horiguchi, S. Kodama et al., Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine, Nature Genetics, vol.43, pp.34-41, 2011.

G. Gagliardi, K. Moroz, and C. F. Bellows, Immunolocalization of DCAMKL-1, a putative intestinal stem cell marker, in normal colonic tissue, Pathol. Res. Pract, vol.208, pp.475-479, 2012.

R. L. Gallo and L. V. Hooper, Epithelial antimicrobial defence of the skin and intestine, Nature Reviews Immunology, vol.12, pp.503-516, 2012.

I. Gantois, R. Ducatelle, F. Pasmans, F. Haesebrouck, I. Hautefort et al., Butyrate specifically down-regulates salmonella pathogenicity island 1 gene expression, Appl. Environ. Microbiol, vol.72, pp.946-949, 2006.

E. M. Garabedian, L. J. Roberts, M. S. Mcnevin, G. , and J. I. , Examining the role of Paneth cells in the small intestine by lineage ablation in transgenic mice, J. Biol. Chem, vol.272, pp.23729-23740, 1997.

J. Geiser, K. J. Venken, R. C. De-lisle, and G. K. Andrews, A mouse model of acrodermatitis enteropathica: loss of intestine zinc transporter ZIP4 (Slc39a4) disrupts the stem cell niche and intestine integrity, PLoS Genet, vol.8, 2012.

F. Gerbe, B. Brulin, L. Makrini, C. Legraverend, J. et al., DCAMKL-1 expression identifies Tuft cells rather than stem cells in the adult mouse intestinal epithelium, Gastroenterology, vol.137, pp.2180-2181, 2009.
URL : https://hal.archives-ouvertes.fr/hal-00434414

F. Gerbe, J. H. Van-es, L. Makrini, B. Brulin, G. Mellitzer et al., Distinct ATOH1 and Neurog3 requirements define tuft cells as a new secretory cell type in the intestinal epithelium, J. Cell Biol, vol.192, pp.767-780, 2011.
URL : https://hal.archives-ouvertes.fr/hal-02459483

F. Gerbe, C. Legraverend, J. , and P. , The intestinal epithelium tuft cells: specification and function, Cell. Mol. Life Sci, vol.69, pp.2907-2917, 2012.
URL : https://hal.archives-ouvertes.fr/hal-02459464

F. Gerbe, E. Sidot, D. J. Smyth, M. Ohmoto, I. Matsumoto et al., Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites, Nature, vol.529, pp.226-230, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01940966

A. Glinka, C. Dolde, N. Kirsch, Y. Huang, O. Kazanskaya et al., LGR4 and LGR5 are R-spondin receptors mediating Wnt/?-catenin and Wnt/PCP signalling, EMBO Rep, vol.12, pp.1055-1061, 2011.

T. Goda, Regulation of the expression of carbohydrate digestion/absorption-related genes, British Journal Of Nutrition, vol.84, pp.245-248, 2000.

R. Goldberg, N. Prescott, G. M. Lord, T. T. Macdonald, P. et al., The unusual suspects--innate lymphoid cells as novel therapeutic targets in IBD, Nat Rev Gastroenterol Hepatol, vol.12, pp.271-283, 2015.

J. Gong, J. Xu, W. Zhu, X. Gao, N. Li et al., Epithelial-specific blockade of MyD88-dependent pathway causes spontaneous small intestinal inflammation, Clin. Immunol, vol.136, pp.245-256, 2010.

N. V. Gorbunov and J. G. Kiang, Up-regulation of autophagy in small intestine Paneth cells in response to total-body gamma-irradiation, J. Pathol, vol.219, pp.242-252, 2009.

N. V. Gorbunov, B. R. Garrison, and J. G. Kiang, Response of crypt paneth cells in the small intestine following total-body gamma-irradiation, Int J Immunopathol Pharmacol, vol.23, pp.1111-1123, 2010.

Y. Goto and H. Kiyono, Epithelial barrier: an interface for the cross-communication between gut flora and immune system, Immunol. Rev, vol.245, pp.147-163, 2012.

A. Gregorieff, D. E. Stange, P. Kujala, H. Begthel, M. Van-den-born et al., The ets-domain transcription factor Spdef promotes maturation of goblet and paneth cells in the intestinal epithelium, Gastroenterology, vol.137, pp.1-3, 2009.

G. Greicius, Z. Kabiri, K. Sigmundsson, C. Liang, R. Bunte et al., PDGFR? + pericryptal stromal cells are the critical source of Wnts and RSPO3 for murine intestinal stem cells in vivo, Proc. Natl. Acad. Sci. U.S.A, vol.115, pp.3173-3181, 2018.

M. Grizotte-lake, G. Zhong, K. Duncan, J. Kirkwood, N. Iyer et al., Commensals Suppress Intestinal Epithelial Cell Retinoic Acid Synthesis to Regulate Interleukin-22 Activity and Prevent Microbial Dysbiosis, Immunity, vol.49, pp.1103-1115, 2018.

A. Hamaï, P. Codogno, and M. Mehrpour, Cancer stem cells and autophagy: Facts and Perspectives, Journal of Cancer Stem Cell Research, vol.2, p.1, 2014.

R. B. Hamanaka and N. S. Chandel, Targeting glucose metabolism for cancer therapy, The Journal of Cell Biology, vol.196, pp.3-3, 2012.

A. M. Hanash, J. A. Dudakov, G. Hua, M. H. O'connor, L. F. Young et al., Interleukin-22 protects intestinal stem cells from immunemediated tissue damage and regulates sensitivity to graft versus host disease, Immunity, vol.37, pp.339-350, 2012.

H. Hao, Y. Xie, Y. Zhang, O. Charlat, E. Oster et al., ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner, Nature, vol.485, pp.195-200, 2012.

A. G. Haramis, H. Begthel, M. Van-den-born, J. Van-es, S. Jonkheer et al., De novo crypt formation and juvenile polyposis on BMP inhibition in mouse intestine, Science, vol.303, pp.1684-1686, 2004.

T. Hattori, H. Eberspaecher, J. Lu, R. Zhang, T. Nishida et al., Interactions between PIAS Proteins and SOX9 Result in an Increase in the Cellular Concentrations of SOX9, J. Biol. Chem, vol.281, pp.14417-14428, 2006.

T. Hattori, T. Kishino, S. Stephen, H. Eberspaecher, S. Maki et al., E6-AP/UBE3A Protein Acts as a Ubiquitin Ligase toward SOX9 Protein, J. Biol. Chem, vol.288, pp.35138-35148, 2013.

X. C. He, J. Zhang, W. Tong, O. Tawfik, J. Ross et al., BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wntbeta-catenin signaling, Nat. Genet, vol.36, pp.1117-1121, 2004.

. Heidenhain, Beitrage zur Histologie und Phpsiologie der Dunndarm-schleimhaut, 1888.

C. Hetz, E. Chevet, and H. P. Harding, Targeting the unfolded protein response in disease, Nature Reviews Drug Discovery, vol.12, pp.703-719, 2013.

Y. Hiramatsu, A. Fukuda, S. Ogawa, N. Goto, K. Ikuta et al., Arid1a is essential for intestinal stem cells through Sox9 regulation, Proceedings of the National Academy of Sciences, vol.116, pp.1704-1713, 2019.

C. M. Hodin, K. Lenaerts, J. Grootjans, J. J. De-haan, M. Hadfoune et al., Starvation compromises Paneth cells, Am. J. Pathol, vol.179, pp.2885-2893, 2011.

B. Hoover, V. Baena, M. M. Kaelberer, F. Getaneh, S. Chinchilla et al., The intestinal tuft cell nanostructure in 3D, Scientific Reports, vol.7, p.1652, 2017.

M. R. Howitt, S. Lavoie, M. Michaud, A. M. Blum, S. V. Tran et al., Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut, Science, vol.351, pp.1329-1333, 2016.

D. W. Huang, B. T. Sherman, and R. A. Lempicki, Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources, Nat Protoc, vol.4, pp.44-57, 2009.

W. Huang, X. Zhou, V. Lefebvre, B. Crombrugghe, and . De, Phosphorylation of SOX9 by Cyclic AMP-Dependent Protein Kinase A Enhances SOX9's Ability To Transactivate aCol2a1 Chondrocyte-Specific Enhancer, Molecular and Cellular Biology, vol.20, pp.4149-4158, 2000.

J. P. Hugot, M. Chamaillard, H. Zouali, S. Lesage, J. P. Cézard et al., Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease, Nature, vol.411, pp.599-603, 2001.

, Structure, function and diversity of the healthy human microbiome, Human Microbiome Project Consortium, vol.486, pp.207-214, 2012.

M. Igarashi and L. Guarente, mTORC1 and SIRT1 Cooperate to Foster Expansion of Gut Adult Stem Cells during Calorie Restriction, Cell, vol.166, pp.436-450, 2016.

T. Ikeda, S. Kamekura, A. Mabuchi, I. Kou, S. Seki et al., The combination of SOX5, SOX6, and SOX9 (the SOX trio) provides signals sufficient for induction of permanent cartilage, Arthritis & Rheumatism, vol.50, pp.3561-3573, 2004.

H. Ireland, R. Kemp, C. Houghton, L. Howard, A. R. Clarke et al., , 2004.

, Inducible Cre-mediated control of gene expression in the murine gastrointestinal tract: effect of loss of beta-catenin, Gastroenterology, vol.126, pp.1236-1246

H. Ireland, C. Houghton, L. Howard, and D. J. Winton, Cellular inheritance of a Cre-activated reporter gene to determine Paneth cell longevity in the murine small intestine, Dev. Dyn, vol.233, pp.1332-1336, 2005.

A. M. Isomäki, A new cell type (tuft cell) in the gastrointestinal mucosa of the rat. A transmission and scanning electron microscopic study, Acta Pathol Microbiol Scand A Suppl, vol.240, pp.1-35, 1973.

K. Ito and K. Ito, Metabolism and the Control of Cell Fate Decisions and Stem Cell Renewal, Annu. Rev. Cell Dev. Biol, vol.32, pp.399-409, 2016.

K. Ito and K. Ito, Metabolism and the Control of Cell Fate Decisions and Stem Cell Renewal, Annual Review of Cell and Developmental Biology, vol.32, pp.399-409, 2016.

S. Itzkovitz, A. Lyubimova, I. C. Blat, M. Maynard, J. Van-es et al., Single-molecule transcript counting of stem-cell markers in the mouse intestine, Nature Cell Biology, vol.14, pp.106-114, 2012.

I. I. Ivanov, K. Atarashi, N. Manel, E. L. Brodie, T. Shima et al., Induction of intestinal Th17 cells by segmented filamentous bacteria, Cell, vol.139, pp.485-498, 2009.

B. M. Javier, R. Yaeger, L. Wang, F. Sanchez-vega, A. Zehir et al., Recurrent, truncating SOX9 mutations are associated with SOX9 overexpression, KRAS mutation, and TP53 wild type status in colorectal carcinoma, Oncotarget, vol.7, 2016.

M. Jenny, C. Uhl, C. Roche, I. Duluc, V. Guillermin et al., Neurogenin3 is differentially required for endocrine cell fate specification in the intestinal and gastric epithelium, EMBO J, vol.21, pp.6338-6347, 2002.

J. Jensen, E. E. Pedersen, P. Galante, J. Hald, R. S. Heller et al., Control of endodermal endocrine development by Hes-1, Nat. Genet, vol.24, pp.36-44, 2000.

H. Jiang, P. H. Patel, A. Kohlmaier, M. O. Grenley, D. G. Mcewen et al., Cytokine/Jak/Stat Signaling Mediates Regeneration and Homeostasis in the Drosophila Midgut, vol.137, pp.1343-1355, 2009.

A. Jo, S. Denduluri, B. Zhang, Z. Wang, L. Yin et al., , 2014.

, The versatile functions of Sox9 in development, stem cells, and human diseases, Genes & Diseases, vol.1, pp.149-161

M. E. Johansson, H. Sjövall, and G. C. Hansson, The gastrointestinal mucus system in health and disease, Nat Rev Gastroenterol Hepatol, vol.10, pp.352-361, 2013.

P. Jung, T. Sato, A. Merlos-suárez, F. M. Barriga, M. Iglesias et al., Isolation and in vitro expansion of human colonic stem cells, Nat. Med, vol.17, pp.1225-1227, 2011.

Z. Kabiri, G. Greicius, B. Madan, S. Biechele, Z. Zhong et al., Stroma provides an intestinal stem cell niche in the absence of epithelial Wnts, Development, vol.141, pp.2206-2215, 2014.

M. Kadaja, B. E. Keyes, M. Lin, H. A. Pasolli, M. Genander et al., SOX9: a stem cell transcriptional regulator of secreted niche signaling factors, Genes & Development, vol.28, pp.328-341, 2014.

G. E. Kaiko, S. H. Ryu, O. I. Koues, P. L. Collins, L. Solnica-krezel et al., The Colonic Crypt Protects Stem Cells from Microbiota-Derived Metabolites, Cell, vol.167, p.1137, 2016.

Y. Kamachi, M. Uchikawa, and H. Kondoh, Pairing SOX off: with partners in the regulation of embryonic development, Trends in Genetics, vol.16, pp.182-187, 2000.

K. Kamdar, S. Khakpour, J. Chen, V. Leone, J. Brulc et al., Genetic and Metabolic Signals during Acute Enteric Bacterial Infection Alter the Microbiota and Drive Progression to Chronic Inflammatory Disease, Cell Host Microbe, vol.19, pp.21-31, 2016.

G. G. Kaplan, The global burden of IBD: from 2015 to 2025, Nature Reviews Gastroenterology & Hepatology, vol.12, pp.720-727, 2015.

P. Katajisto, J. Döhla, C. L. Chaffer, N. Pentinmikko, N. Marjanovic et al., Stem cells. Asymmetric apportioning of aged mitochondria between daughter cells is required for stemness, Science, vol.348, pp.340-343, 2015.

J. P. Katz, N. Perreault, B. G. Goldstein, C. S. Lee, P. A. Labosky et al., The zinc-finger transcription factor Klf4 is required for terminal differentiation of goblet cells in the colon, Development, vol.129, pp.2619-2628, 2002.

K. Kemper, P. R. Prasetyanti, W. De-lau, H. Rodermond, H. Clevers et al., Monoclonal antibodies against Lgr5 identify human colorectal cancer stem cells, Stem Cells, vol.30, pp.2378-2386, 2012.

Y. S. Kim and S. B. Ho, Intestinal goblet cells and mucins in health and disease: recent insights and progress, Curr Gastroenterol Rep, vol.12, pp.319-330, 2010.

S. C. Kim, S. L. Tonkonogy, C. A. Albright, J. Tsang, E. J. Balish et al., Variable phenotypes of enterocolitis in interleukin 10-deficient mice monoassociated with two different commensal bacteria, Gastroenterology, vol.128, pp.891-906, 2005.

Y. Kim, Y. Lee, S. W. Kang, S. Kim, T. Kim et al., Loss of PKM2 in Lgr5+ intestinal stem cells promotes colitis-associated colorectal cancer, 2019.

R. Kist, H. Schrewe, R. Balling, and G. Scherer, Conditional inactivation of Sox9: a mouse model for campomelic dysplasia, Genesis, vol.32, pp.121-123, 2002.

K. A. Knoop, N. Kumar, B. R. Butler, S. K. Sakthivel, R. T. Taylor et al., RANKL is necessary and sufficient to initiate development of antigensampling M cells in the intestinal epithelium, J. Immunol, vol.183, pp.5738-5747, 2009.

K. S. Kobayashi, M. Chamaillard, Y. Ogura, O. Henegariu, N. Inohara et al., Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract, Science, vol.307, pp.731-734, 2005.

B. Koo, M. Spit, I. Jordens, T. Y. Low, D. E. Stange et al., Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors, Nature, vol.488, pp.665-669, 2012.

V. Korinek, N. Barker, K. Willert, M. Molenaar, J. Roose et al., Two Members of the Tcf Family Implicated in Wnt/?-Catenin Signaling during Embryogenesis in the Mouse, Molecular and Cellular Biology, vol.18, pp.1248-1256, 1998.

C. Kosinski, V. S. Li, A. S. Chan, J. Zhang, C. Ho et al., Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors, PNAS, vol.104, pp.15418-15423, 2007.

C. Kosinski, D. E. Stange, C. Xu, A. S. Chan, C. Ho et al., Indian hedgehog regulates intestinal stem cell fate through epithelialmesenchymal interactions during development, Gastroenterology, vol.139, pp.893-903, 2010.

R. A. Kovall, B. Gebelein, D. Sprinzak, and R. Kopan, The Canonical Notch Signaling Pathway: Structural and Biochemical Insights into Shape, Sugar, and Force, Developmental Cell, vol.41, pp.228-241, 2017.

S. Kozar, E. Morrissey, A. M. Nicholson, M. Van-der-heijden, H. I. Zecchini et al., Continuous Clonal Labeling Reveals Small Numbers of Functional Stem Cells in Intestinal Crypts and Adenomas, Cell Stem Cell, vol.13, pp.626-633, 2013.

F. Kuhnert, C. R. Davis, H. Wang, P. Chu, M. Lee et al., Essential requirement for Wnt signaling in proliferation of adult small intestine and colon revealed by adenoviral expression of Dickkopf-1, PNAS, vol.101, pp.266-271, 2004.

L. Vecchia, S. Sebastián, and C. , Metabolic pathways regulating colorectal cancer initiation and progression, Seminars in Cell & Developmental Biology, 2019.

B. Lamas, M. L. Richard, V. Leducq, H. Pham, M. Michel et al., CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands, Nature Medicine, vol.22, pp.598-605, 2016.
URL : https://hal.archives-ouvertes.fr/hal-02796262

A. D. Lander, J. Kimble, H. Clevers, E. Fuchs, D. Montarras et al., What does the concept of the stem cell niche really mean today?, BMC Biol, vol.10, p.19, 2012.
URL : https://hal.archives-ouvertes.fr/pasteur-00677814

W. De-lau, N. Barker, T. Y. Low, B. Koo, V. S. Li et al., Lgr5 homologues associate with Wnt receptors and mediate Rspondin signalling, Nature, vol.476, pp.293-297, 2011.

W. De-lau, P. Kujala, K. Schneeberger, S. Middendorp, V. S. Li et al., Peyer's patch M cells derived from Lgr5(+) stem cells require SpiB and are induced by RankL in cultured "miniguts, Mol. Cell. Biol, vol.32, pp.3639-3647, 2012.

C. P. Leblond and C. E. Stevens, The constant renewal of the intestinal epithelium in the albino rat, The Anatomical Record, vol.100, pp.357-377, 1948.

C. Lee, B. G. Kim, J. H. Kim, J. Chun, J. P. Im et al., Sodium butyrate inhibits the NF-kappa B signaling pathway and histone deacetylation, and attenuates experimental colitis in an IL-10 independent manner, Int. Immunopharmacol, vol.51, pp.47-56, 2017.

Y. Lee, T. Kim, Y. Kim, S. Lee, S. Kim et al., Microbiota-Derived Lactate Accelerates Intestinal Stem-Cell-Mediated Epithelial Development, Cell Host & Microbe, vol.24, pp.833-846, 2018.

W. Lei, W. Ren, M. Ohmoto, J. F. Urban, I. Matsumoto et al., Activation of intestinal tuft cell-expressed Sucnr1 triggers type 2 immunity in the mouse small intestine, Proc. Natl. Acad. Sci. U.S.A, vol.115, pp.5552-5557, 2018.

V. Leone, E. B. Chang, and S. Devkota, Diet, microbes, and host genetics: the perfect storm in inflammatory bowel diseases, J. Gastroenterol, vol.48, pp.315-321, 2013.

V. Y. Leung, B. Gao, K. K. Leung, I. G. Melhado, S. L. Wynn et al., SOX9 Governs Differentiation Stage-Specific Gene Expression in Growth Plate Chondrocytes via Direct Concomitant Transactivation and Repression, PLOS Genetics, vol.7, 2011.

P. A. Li, X. Hou, and S. Hao, Mitochondrial biogenesis in neurodegeneration, J. Neurosci. Res, vol.95, pp.2025-2029, 2017.

M. Y. Lin, M. R. De-zoete, J. P. Van-putten, and K. Strijbis, Redirection of Epithelial Immune Responses by Short-Chain Fatty Acids through Inhibition of Histone Deacetylases, Front Immunol, vol.6, p.554, 2015.

C. A. Lindemans, M. Calafiore, A. M. Mertelsmann, M. H. O'connor, J. A. Dudakov et al., Interleukin-22 promotes intestinal-stem-cellmediated epithelial regeneration, Nature, vol.528, pp.560-564, 2015.

J. A. Liu, M. Wu, C. H. Yan, B. K. Chau, H. So et al., Phosphorylation of Sox9 is required for neural crest delamination and is regulated downstream of BMP and canonical Wnt signaling, PNAS, vol.110, pp.2882-2887, 2013.

W. Liu, L. Chen, J. Zhu, and G. P. Rodgers, The glycoprotein hGC-1 binds to cadherin and lectins, Exp. Cell Res, vol.312, pp.1785-1797, 2006.

W. Liu, H. Li, S. Hong, G. P. Piszczek, W. Chen et al., Olfactomedin 4 deletion induces colon adenocarcinoma in Apc Min/+ mice, Oncogene, vol.35, pp.5237-5247, 2016.

L. López-díaz, R. N. Jain, T. M. Keeley, K. L. Vandussen, C. S. Brunkan et al., Intestinal Neurogenin 3 directs differentiation of a bipotential secretory progenitor to endocrine cell rather than goblet cell fate, Dev. Biol, vol.309, pp.298-305, 2007.

C. Lopez-garcia, A. M. Klein, B. D. Simons, and D. J. Winton, Intestinal Stem Cell Replacement Follows a Pattern of Neutral Drift, Science, vol.330, pp.822-825, 2010.

B. Lü, Y. Fang, J. Xu, L. Wang, F. Xu et al., Analysis of SOX9 expression in colorectal cancer, Am. J. Clin. Pathol, vol.130, pp.897-904, 2008.

Y. Lu, X. Li, S. Liu, Y. Zhang, and D. Zhang, Toll-like Receptors and Inflammatory Bowel Disease, 2018.

N. Y. Lycke and M. Bemark, The regulation of gut mucosal IgA B-cell responses: recent developments, Mucosal Immunol, vol.10, pp.1361-1374, 2017.

A. J. Macpherson and N. L. Harris, Interactions between commensal intestinal bacteria and the immune system, Nature Reviews Immunology, vol.4, pp.478-485, 2004.

N. Maharshak, C. D. Packey, M. Ellermann, S. Manick, J. P. Siddle et al., Altered enteric microbiota ecology in interleukin 10-deficient mice during development and progression of intestinal inflammation, Gut Microbes, vol.4, pp.316-324, 2013.

M. D. Mana, E. Y. Kuo, .. Yilmaz, and Ö. H. , Dietary Regulation of Adult Stem Cells, Curr Stem Cell Rep, vol.3, pp.1-8, 2017.

F. El-marjou, K. Janssen, B. H. Chang, .. Li, M. Hindie et al., Tissue-specific and inducible Cre-mediated recombination in the gut epithelium, Genesis, vol.39, pp.186-193, 2004.

E. Marshman, C. Booth, and C. S. Potten, The intestinal epithelial stem cell, BioEssays, vol.24, pp.91-98, 2002.

M. Matano, S. Date, M. Shimokawa, A. Takano, M. Fujii et al., Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids, Nat. Med, vol.21, pp.256-262, 2015.

C. L. May and K. H. Kaestner, Gut endocrine cell development, Molecular and Cellular Endocrinology, vol.323, pp.70-75, 2010.

R. May, S. M. Sureban, N. Hoang, T. E. Riehl, S. A. Lightfoot et al., Doublecortin and CaM kinase-like-1 and leucine-rich-repeat-containing Gprotein-coupled receptor mark quiescent and cycling intestinal stem cells, respectively, Stem Cells, vol.27, pp.2571-2579, 2009.

Q. Mcafee, Z. Zhang, A. Samanta, S. M. Levi, X. Ma et al., Autophagy inhibitor Lys05 has single-agent antitumor activity and reproduces the phenotype of a genetic autophagy deficiency, Proc. Natl. Acad. Sci. U.S.A, vol.109, pp.8253-8258, 2012.

M. Mcfall-ngai, M. G. Hadfield, T. C. Bosch, H. V. Carey, T. Domazet-lo?o et al., Animals in a bacterial world, a new imperative for the life sciences, Proc. Natl. Acad. Sci. U.S.A, vol.110, pp.3229-3236, 2013.
URL : https://hal.archives-ouvertes.fr/hal-00972300

G. Mellitzer, A. Beucher, V. Lobstein, P. Michel, S. Robine et al., Loss of enteroendocrine cells in mice alters lipid absorption and glucose homeostasis and impairs postnatal survival, J. Clin. Invest, vol.120, pp.1708-1721, 2010.

A. Merlos-suárez, F. M. Barriga, P. Jung, M. Iglesias, M. V. Céspedes et al., The Intestinal Stem Cell Signature Identifies Colorectal Cancer Stem Cells and Predicts Disease Relapse, Cell Stem Cell, vol.8, pp.511-524, 2011.

S. Middendorp, K. Schneeberger, C. L. Wiegerinck, M. Mokry, R. D. Akkerman et al., Adult stem cells in the small intestine are intrinsically programmed with their location-specific function, Stem Cells, vol.32, pp.1083-1091, 2014.

M. M. Mihaylova and R. J. Shaw, The AMPK signalling pathway coordinates cell growth, autophagy and metabolism, Nature Cell Biology, vol.13, pp.1016-1023, 2011.

M. M. Mihaylova, C. Cheng, A. Q. Cao, S. Tripathi, M. D. Mana et al., Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging, Cell Stem Cell, vol.22, pp.769-778, 2018.

N. Mizushima, T. Yoshimori, and Y. Ohsumi, The role of Atg proteins in autophagosome formation, Annu. Rev. Cell Dev. Biol, vol.27, pp.107-132, 2011.

J. Von-moltke, M. Ji, H. Liang, and R. M. Locksley, Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit, Nature, vol.529, pp.221-225, 2016.

R. K. Montgomery, D. L. Carlone, C. A. Richmond, L. Farilla, M. E. Kranendonk et al., Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells, Proc. Natl. Acad. Sci. U.S.A, vol.108, pp.179-184, 2011.

M. E. Morgan, P. J. Koelink, B. Zheng, M. H. Den-brok, H. J. Van-de-kant et al., Toll-like receptor 6 stimulation promotes Thelper 1 and 17 responses in gastrointestinal-associated lymphoid tissue and modulates murine experimental colitis, Mucosal Immunol, vol.7, pp.1266-1277, 2014.

Y. Mori-akiyama, M. Van-den-born, J. H. Van-es, S. R. Hamilton, H. P. Adams et al., SOX9 is required for the differentiation of paneth cells in the intestinal epithelium, Gastroenterology, vol.133, pp.539-546, 2007.

S. Mukherjee and L. V. Hooper, Antimicrobial Defense of the Intestine, Immunity, vol.42, pp.28-39, 2015.

J. Muñoz, D. E. Stange, A. G. Schepers, M. Van-de-wetering, B. Koo et al., The Lgr5 intestinal stem cell signature: robust expression of proposed quiescent '+4' cell markers: Transcriptomic and proteomic signature of Lgr5 + stem cells, The EMBO Journal, vol.31, pp.3079-3091, 2012.

L. M. Murray and A. D. Krasnodembskaya, Concise Review: Intercellular Communication Via Organelle Transfer in the Biology and Therapeutic Applications of Stem Cells: Intercellular Communication Via Organelle Transfer, STEM CELLS, vol.37, pp.14-25, 2019.

M. S. Nadjsombati, J. W. Mcginty, M. R. Lyons-cohen, J. B. Jaffe, L. Dipeso et al., Detection of Succinate by Intestinal Tuft Cells Triggers a Type 2 Innate Immune Circuit, Immunity, vol.49, pp.33-41, 2018.

Y. Nakanishi, H. Seno, A. Fukuoka, T. Ueo, Y. Yamaga et al., Dclk1 distinguishes between tumor and normal stem cells in the intestine, Nat. Genet, vol.45, pp.98-103, 2013.

M. D. Neal, C. P. Sodhi, H. Jia, M. Dyer, C. E. Egan et al., Toll-like receptor 4 is expressed on intestinal stem cells and regulates their proliferation and apoptosis via the p53 up-regulated modulator of apoptosis, J. Biol. Chem, vol.287, pp.37296-37308, 2012.

G. Nigro, R. Rossi, P. Commere, P. Jay, and P. J. Sansonetti, The cytosolic bacterial peptidoglycan sensor Nod2 affords stem cell protection and links microbes to gut epithelial regeneration, Cell Host Microbe, vol.15, pp.792-798, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01950138

Z. Noor, S. L. Burgess, K. Watanabe, and W. A. Jr, Interleukin-25 Mediated Induction of Angiogenin-4 Is Interleukin-13 Dependent, PLOS ONE, vol.11, p.153572, 2016.

Y. Ogura, D. K. Bonen, N. Inohara, D. L. Nicolae, F. F. Chen et al., A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease, Nature, vol.411, pp.603-606, 2001.

Y. Ogura, S. Lala, W. Xin, E. Smith, T. A. Dowds et al., Expression of NOD2 in Paneth cells: a possible link to Crohn's ileitis, Gut, vol.52, pp.1591-1597, 2003.

H. J. Oh, T. Kido, and Y. C. Lau, PIAS1 interacts with and represses SOX9 transactivation activity, Molecular Reproduction and Development, vol.74, pp.1446-1455, 2007.

T. Okada, S. Fukuda, K. Hase, S. Nishiumi, Y. Izumi et al., Microbiota-derived lactate accelerates colon epithelial cell turnover in starvation-refed mice, Nat Commun, vol.4, p.1654, 2013.

K. O'rourke, L. Dow, and S. Lowe, Immunofluorescent Staining of Mouse Intestinal Stem Cells, BIO-PROTOCOL, vol.6, 2016.

O. Pabst, New concepts in the generation and functions of IgA, Nat. Rev. Immunol, vol.12, pp.821-832, 2012.

O. Pabst, H. Herbrand, M. Friedrichsen, S. Velaga, M. Dorsch et al., Adaptation of solitary intestinal lymphoid tissue in response to microbiota and chemokine receptor CCR7 signaling, J. Immunol, vol.177, pp.6824-6832, 2006.

. Paneth, Ueber die secernirenden Zellen des Diinndarm-Epithels. Mikr, pp.113-191, 1888.

A. Panza, V. Pazienza, M. Ripoli, G. Benegiamo, A. Gentile et al., Interplay between SOX9, ?-catenin and PPAR? activation in colorectal cancer, Biochimica et Biophysica Acta (BBA) -Molecular Cell Research, vol.1833, pp.1853-1865, 2013.

F. Paris, Z. Fuks, A. Kang, P. Capodieci, G. Juan et al., Endothelial apoptosis as the primary lesion initiating intestinal radiation damage in mice, Science, vol.293, pp.293-297, 2001.

B. C. Peck, J. Sincavage, S. Feinstein, A. T. Mah, J. G. Simmons et al., miR-30 Family Controls Proliferation and Differentiation of Intestinal Epithelial Cell Models by Directing a Broad Gene Expression Program That Includes SOX9 and the Ubiquitin Ligase Pathway, Journal of Biological Chemistry, vol.291, pp.15975-15984, 2016.

B. Pêgo, C. A. Martinusso, C. Bernardazzi, B. E. Ribeiro, A. F. De-araujo-cunha et al., Schistosoma mansoni Coinfection Attenuates Murine Toxoplasma gondii-Induced Crohn's-Like Ileitis by Preserving the Epithelial Barrier and Downregulating the Inflammatory Response, Frontiers in Immunology, vol.10, 2019.

T. Pelaseyed, J. H. Bergström, J. K. Gustafsson, A. Ermund, G. M. Birchenough et al., The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system, Immunological Reviews, vol.260, pp.8-20, 2014.

L. Pellegrinet, V. Rodilla, Z. Liu, S. Chen, U. Koch et al., Dll1-and dll4-mediated notch signaling are required for homeostasis of intestinal stem cells, Gastroenterology, vol.140, pp.1-7, 2011.

L. Peng, Z. Li, R. S. Green, I. R. Holzman, L. et al., Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers, J. Nutr, vol.139, pp.1619-1625, 2009.

T. Petnicki-ocwieja, T. Hrncir, Y. Liu, A. Biswas, T. Hudcovic et al., Nod2 is required for the regulation of commensal microbiota in the intestine, Proc. Natl. Acad. Sci. U.S.A, vol.106, pp.15813-15818, 2009.

T. A. Pham and T. D. Lawley, Emerging insights on intestinal dysbiosis during bacterial infections, Current Opinion in Microbiology, vol.17, pp.67-74, 2014.

T. Piche, G. Barbara, P. Aubert, S. Bruley-des-varannes, R. Dainese et al., Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators, Gut, vol.58, pp.196-201, 2009.
URL : https://hal.archives-ouvertes.fr/inserm-00332066

G. Pickert, C. Neufert, M. Leppkes, Y. Zheng, N. Wittkopf et al., STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing, J. Exp. Med, vol.206, pp.1465-1472, 2009.

D. Pinto, A. Gregorieff, H. Begthel, and H. Clevers, Canonical Wnt signals are essential for homeostasis of the intestinal epithelium, Genes Dev, vol.17, pp.1709-1713, 2003.

C. S. Potten, Extreme sensitivity of some intestinal crypt cells to X and ? irradiation, Nature, vol.269, p.518, 1977.

C. S. Potten, L. Kovacs, H. , and E. , Continuous labelling studies on mouse skin and intestine, Cell Tissue Kinet, vol.7, pp.271-283, 1974.

C. S. Potten, C. Booth, and D. M. Pritchard, The intestinal epithelial stem cell: the mucosal governor, Int J Exp Pathol, vol.78, pp.219-243, 1997.

G. A. Preidis, D. M. Saulnier, S. E. Blutt, T. Mistretta, K. P. Riehle et al., Probiotics stimulate enterocyte migration and microbial diversity in the neonatal mouse intestine, The FASEB Journal, vol.26, pp.1960-1969, 2012.

C. Prévostel and P. Blache, The dose-dependent effect of SOX9 and its incidence in colorectal cancer, European Journal of Cancer, vol.86, pp.150-157, 2017.

C. Prévostel, C. Rammah-bouazza, H. Trauchessec, L. Canterel-thouennon, M. Busson et al., SOX9 is an atypical intestinal tumor suppressor controlling the oncogenic Wnt/ß-catenin signaling, Oncotarget, vol.7, 2016.

J. Pritchett, V. Athwal, N. Roberts, N. A. Hanley, and K. P. Hanley, Understanding the role of SOX9 in acquired diseases: lessons from development, Trends in Molecular Medicine, vol.17, pp.166-174, 2011.

M. Puzan, S. Hosic, C. Ghio, and A. Koppes, Enteric Nervous System Regulation of Intestinal Stem Cell Differentiation and Epithelial Monolayer Function, 2018.

Y. Qian, S. Xia, and Z. Feng, Sox9 mediated transcriptional activation of FOXK2 is critical for colorectal cancer cells proliferation, Biochemical and Biophysical Research Communications, vol.483, pp.475-481, 2017.

J. Qin, R. Li, J. Raes, M. Arumugam, K. S. Burgdorf et al., A human gut microbial gene catalogue established by metagenomic sequencing, Nature, vol.464, pp.59-65, 2010.
URL : https://hal.archives-ouvertes.fr/cea-00908974

S. Rakoff-nahoum, J. Paglino, F. Eslami-varzaneh, S. Edberg, and R. Medzhitov, Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis, Cell, vol.118, pp.229-241, 2004.

M. Rao, D. Rastelli, L. Dong, S. Chiu, W. Setlik et al., Enteric Glia Regulate Gastrointestinal Motility but Are Not Required for Maintenance of the Epithelium in Mice, Gastroenterology, vol.153, pp.1068-1081, 2017.

E. Rath, A. Moschetta, and D. Haller, Mitochondrial function -gatekeeper of intestinal epithelial cell homeostasis, Nature Reviews Gastroenterology & Hepatology, vol.15, pp.497-516, 2018.

A. Reddy and B. Fried, An update on the use of helminths to treat Crohn's and other autoimmunune diseases, Parasitol. Res, vol.104, pp.217-221, 2009.

M. Rera, S. Bahadorani, J. Cho, C. L. Koehler, M. Ulgherait et al., Modulation of Longevity and Tissue Homeostasis by the Drosophila PGC-1, 2011.
URL : https://hal.archives-ouvertes.fr/hal-02347344

. Homolog, Cell Metabolism, vol.14, pp.623-634

A. Riba, M. Olier, S. Lacroix-lamandé, C. Lencina, V. Bacquié et al., Paneth Cell Defects Induce Microbiota Dysbiosis in Mice and Promote Visceral Hypersensitivity, Gastroenterology, vol.153, pp.1594-1606, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01603303

L. Ritsma, S. I. Ellenbroek, A. Zomer, H. J. Snippert, F. J. De-sauvage et al., Intestinal crypt homeostasis revealed at single stem cell level by in vivo liveimaging, Nature, vol.507, pp.362-365, 2014.

S. A. Roberts, J. H. Hendry, and C. S. Potten, Deduction of the clonogen content of intestinal crypts: a direct comparison of two-dose and multiple-dose methodologies, Radiat. Res, vol.141, pp.303-308, 1995.

K. C. Roche, A. D. Gracz, X. F. Liu, V. Newton, H. Akiyama et al., SOX9 Maintains Reserve Stem Cells and Preserves Radioresistance in Mouse Small Intestine, Gastroenterology, vol.149, pp.1553-1563, 2015.

G. Roda, Intestinal epithelial cells in inflammatory bowel diseases, World Journal of Gastroenterology, vol.16, p.4264, 2010.

M. J. Rodríguez-colman, M. Schewe, M. Meerlo, E. Stigter, J. Gerrits et al., Interplay between metabolic identities in the intestinal crypt supports stem cell function, Nature, vol.543, pp.424-427, 2017.

M. E. Rothenberg, Y. Nusse, T. Kalisky, J. J. Lee, P. Dalerba et al., Identification of a cKit(+) colonic crypt base secretory cell that supports Lgr5(+) stem cells in mice, Gastroenterology, vol.142, pp.1195-1205, 2012.

M. Roulis and R. A. Flavell, Fibroblasts and myofibroblasts of the intestinal lamina propria in physiology and disease, Differentiation, vol.92, pp.116-131, 2016.

C. Rumio, D. Besusso, M. Palazzo, S. Selleri, L. Sfondrini et al., Degranulation of paneth cells via toll-like receptor 9, Am. J. Pathol, vol.165, pp.373-381, 2004.

C. Rumio, M. Sommariva, L. Sfondrini, M. Palazzo, D. Morelli et al., Induction of Paneth cell degranulation by orally administered Toll-like receptor ligands, J. Cell. Physiol, vol.227, pp.1107-1113, 2012.

S. Saha, E. Aranda, Y. Hayakawa, P. Bhanja, S. Atay et al., Macrophage-derived extracellular vesicle-packaged WNTs rescue intestinal stem cells and enhance survival after radiation injury, Nat Commun, vol.7, p.13096, 2016.

B. S. Sailaja, X. C. He, L. , and L. , The regulatory niche of intestinal stem cells: Regulatory niche of intestinal stem cells, The Journal of Physiology, vol.594, pp.4827-4836, 2016.

N. H. Salzman, Paneth cell defensins and the regulation of the microbiome: détente at mucosal surfaces, Gut Microbes, vol.1, pp.401-406, 2010.

N. H. Salzman and C. L. Bevins, Dysbiosis--a consequence of Paneth cell dysfunction, Semin. Immunol, vol.25, pp.334-341, 2013.

N. H. Salzman, D. Ghosh, K. M. Huttner, Y. Paterson, and C. L. Bevins, Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin, Nature, vol.422, pp.522-526, 2003.

N. H. Salzman, M. A. Underwood, and C. L. Bevins, Paneth cells, defensins, and the commensal microbiota: a hypothesis on intimate interplay at the intestinal mucosa, Semin. Immunol, vol.19, pp.70-83, 2007.

N. H. Salzman, K. Hung, D. Haribhai, H. Chu, J. Karlsson-sjöberg et al., Enteric defensins are essential regulators of intestinal microbial ecology, Nat. Immunol, vol.11, pp.76-83, 2010.

E. Sangiorgi and M. R. Capecchi, Bmi1 is expressed in vivo in intestinal stem cells, Nat. Genet, vol.40, pp.915-920, 2008.

A. K. San-roman, C. D. Jayewickreme, L. C. Murtaugh, and R. A. Shivdasani, Wnt Secretion from Epithelial Cells and Subepithelial Myofibroblasts Is Not Required in the Mouse Intestinal Stem Cell Niche In Vivo, Stem Cell Reports, vol.2, pp.127-134, 2014.

N. Sasaki, N. Sachs, K. Wiebrands, S. I. Ellenbroek, A. Fumagalli et al., Reg4+ deep crypt secretory cells function as epithelial niche for Lgr5+ stem cells in colon, PNAS, vol.113, pp.5399-5407, 2016.

T. Sato, R. G. Vries, H. J. Snippert, M. Van-de-wetering, N. Barker et al., Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche, Nature, vol.459, pp.262-265, 2009.

T. Sato, J. H. Van-es, H. J. Snippert, D. E. Stange, R. G. Vries et al., Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts, Nature, vol.469, pp.415-418, 2011.

T. Sato, D. E. Stange, M. Ferrante, R. G. Vries, J. H. Van-es et al., Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium, Gastroenterology, vol.141, pp.1762-1772, 2011.

Y. Satoh, Atropine inhibits the degranulation of Paneth cells in ex-germ-free mice, Cell Tissue Res, vol.253, pp.397-402, 1988.

J. C. Schell, D. R. Wisidagama, C. Bensard, H. Zhao, P. Wei et al., Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism, Nature Cell Biology, vol.19, pp.1027-1036, 2017.

C. Schneider, C. E. O'leary, J. Von-moltke, H. Liang, Q. Y. Ang et al., A Metabolite-Triggered Tuft Cell-ILC2 Circuit Drives Small Intestinal Remodeling, Cell, vol.174, pp.271-284, 2018.

J. Schuijers, J. P. Junker, M. Mokry, P. Hatzis, B. Koo et al., Ascl2 acts as an R-spondin/Wnt-responsive switch to control stemness in intestinal crypts, Cell Stem Cell, vol.16, pp.158-170, 2015.

G. Schwank, B. Koo, V. Sasselli, J. F. Dekkers, I. Heo et al., Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients, Cell Stem Cell, vol.13, pp.653-658, 2013.

C. E. Scott, S. L. Wynn, A. Sesay, C. Cruz, M. Cheung et al., SOX9 induces and maintains neural stem cells, vol.13, pp.1181-1189, 2010.
URL : https://hal.archives-ouvertes.fr/hal-00580084

R. Sekido and R. Lovell-badge, Sex determination involves synergistic action of SRY and SF1 on a specific Sox9 enhancer, Nature, vol.453, pp.930-934, 2008.

P. A. Seymour, K. K. Freude, M. N. Tran, E. E. Mayes, J. Jensen et al., SOX9 is required for maintenance of the pancreatic progenitor cell pool, Proc. Natl. Acad. Sci. U.S.A, vol.104, pp.1865-1870, 2007.

M. T. Shanahan, I. M. Carroll, E. Grossniklaus, A. White, R. J. Von-furstenberg et al., Mouse Paneth cell antimicrobial function is independent of Nod2, Gut, vol.63, pp.903-910, 2014.

Z. Shen, H. Deng, Y. Fang, X. Zhu, G. Ye et al., Identification of the interplay between SOX9 and S100P in the metastasis and invasion of colon carcinoma, Oncotarget, vol.6, pp.20672-20684, 2015.

Z. Shi, C. Chiang, T. Mistretta, A. Major, and Y. Mori-akiyama, SOX9 directly regulates IGFBP-4 in the intestinal epithelium, American Journal of Physiology-Gastrointestinal and Liver Physiology, vol.305, pp.74-83, 2013.

Z. Shi, C. Chiang, T. Mistretta, A. Major, and Y. Mori-akiyama, SOX9 directly regulates IGFBP-4 in the intestinal epithelium, American Journal of Physiology-Gastrointestinal and Liver Physiology, vol.305, pp.74-83, 2013.

Z. Shi, C. Chiang, P. Labhart, Y. Zhao, J. Yang et al., Context-specific role of SOX9 in NF-Y mediated gene regulation in colorectal cancer cells, Nucleic Acids Res, vol.43, pp.6257-6269, 2015.

M. Shimokawa, Y. Ohta, S. Nishikori, M. Matano, A. Takano et al., Visualization and targeting of LGR5+ human colon cancer stem cells, Nature, vol.545, pp.187-192, 2017.

M. Shoshkes-carmel, Y. J. Wang, K. J. Wangensteen, B. Tóth, A. Kondo et al., Subepithelial telocytes are an important source of Wnts that supports intestinal crypts, Nature, vol.557, p.242, 2018.

N. F. Shroyer, M. A. Helmrath, V. Y. Wang, .. Antalffy, B. Henning et al., Intestinespecific ablation of mouse atonal homolog 1 (Math1) reveals a role in cellular homeostasis, Gastroenterology, vol.132, pp.2478-2488, 2007.

L. A. Simms, J. D. Doecke, R. L. Roberts, E. V. Fowler, Z. Z. Zhao et al., KCNN4 gene variant is associated with ileal Crohn's Disease in the Australian and New Zealand population, Am. J. Gastroenterol, vol.105, pp.2209-2217, 2010.

B. D. Simons and H. Clevers, Strategies for Homeostatic Stem Cell Self-Renewal in Adult Tissues, Cell, vol.145, pp.851-862, 2011.

K. Smith, K. D. Mccoy, and A. J. Macpherson, Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota, Semin. Immunol, vol.19, pp.59-69, 2007.

H. J. Snippert, L. G. Van-der-flier, T. Sato, J. H. Van-es, M. Van-den-born et al., Intestinal Crypt Homeostasis Results from Neutral Competition between Symmetrically Dividing Lgr5 Stem Cells, Cell, vol.143, pp.134-144, 2010.

G. F. Sonnenberg and D. Artis, Innate lymphoid cells in the initiation, regulation and resolution of inflammation, Nature Medicine, vol.21, pp.698-708, 2015.

G. F. Sonnenberg and D. Artis, Innate lymphoid cells in the initiation, regulation and resolution of inflammation, Nature Medicine, vol.21, pp.698-708, 2015.

F. De-sousa-e-melo, A. V. Kurtova, J. M. Harnoss, N. Kljavin, J. D. Hoeck et al., A distinct role for Lgr5+ stem cells in primary and metastatic colon cancer, Nature, vol.543, pp.676-680, 2017.

H. S. De-souza and C. Fiocchi, Immunopathogenesis of IBD: current state of the art, Nature Reviews Gastroenterology & Hepatology, vol.13, pp.13-27, 2016.

T. S. Stappenbeck, The role of autophagy in Paneth cell differentiation and secretion, Mucosal Immunol, vol.3, pp.8-10, 2010.

M. D. Stobbe, S. M. Houten, A. H. Van-kampen, R. J. Wanders, and P. D. Moerland, Improving the description of metabolic networks: the TCA cycle as example, FASEB J, vol.26, pp.3625-3636, 2012.

E. E. Storm, S. Durinck, F. De-sousa-e-melo, J. Tremayne, N. Kljavin et al., Targeting PTPRK-RSPO3 colon tumours promotes differentiation and loss of stem-cell function, Nature, vol.529, pp.97-100, 2016.

I. Stzepourginski, G. Nigro, J. Jacob, S. Dulauroy, P. J. Sansonetti et al., CD34+ mesenchymal cells are a major component of the intestinal stem cells niche at homeostasis and after injury, Proc. Natl. Acad. Sci. U.S.A, vol.114, pp.506-513, 2017.
URL : https://hal.archives-ouvertes.fr/pasteur-01449402

J. Su, T. Chen, X. Ji, C. Liu, P. K. Yadav et al., IL-25 downregulates Th1/Th17 immune response in an IL-10-dependent manner in inflammatory bowel disease, Inflamm. Bowel Dis, vol.19, pp.720-728, 2013.

A. Subramanian, P. Tamayo, V. K. Mootha, S. Mukherjee, B. L. Ebert et al., Gene set enrichment analysis: a knowledgebased approach for interpreting genome-wide expression profiles, Proc. Natl. Acad. Sci. U.S.A, vol.102, pp.15545-15550, 2005.

M. Sun, W. Wu, Z. Liu, and Y. Cong, Microbiota metabolite short chain fatty acids, GPCR, and inflammatory bowel diseases, Journal of Gastroenterology, vol.52, pp.1-8, 2017.

N. Takeda, R. Jain, M. R. Leboeuf, Q. Wang, M. M. Lu et al., Interconversion Between Intestinal Stem Cell Populations in Distinct Niches, Science, vol.334, pp.1420-1424, 2011.

S. Tamburini, N. Shen, H. C. Wu, C. , and J. C. , The microbiome in early life: implications for health outcomes, Nature Medicine, vol.22, pp.713-722, 2016.

H. Tanabe, T. Ayabe, B. Bainbridge, T. Guina, R. K. Ernst et al., Mouse paneth cell secretory responses to cell surface glycolipids of virulent and attenuated pathogenic bacteria, Infect. Immun, vol.73, pp.2312-2320, 2005.

K. M. Taylor and C. Labonne, SoxE Factors Function Equivalently during Neural Crest and Inner Ear Development and Their Activity Is Regulated by SUMOylation, Developmental Cell, vol.9, pp.593-603, 2005.

P. W. Tetteh, O. Basak, H. F. Farin, K. Wiebrands, K. Kretzschmar et al., Replacement of Lost Lgr5-Positive Stem Cells through Plasticity of Their Enterocyte-Lineage Daughters, Cell Stem Cell, vol.18, pp.203-213, 2016.

P. D. Thomas, A. Kejariwal, M. J. Campbell, H. Mi, K. Diemer et al., PANTHER: a browsable database of gene products organized by biological function, using curated protein family and subfamily classification, Nucleic Acids Res, vol.31, pp.334-341, 2003.

S. Thomas, J. Izard, E. Walsh, K. Batich, P. Chongsathidkiet et al., The Host Microbiome Regulates and Maintains Human Health: A Primer and Perspective for Non-Microbiologists, Cancer Research, vol.77, pp.1783-1812, 2017.

H. Tian, B. Biehs, S. Warming, K. G. Leong, L. Rangell et al., A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable, Nature, vol.478, pp.255-259, 2011.

H. Ting and J. Von-moltke, The Immune Function of Tuft Cells at Gut Mucosal Surfaces and Beyond, The Journal of Immunology, vol.202, pp.1321-1329, 2019.

C. Tropini, K. A. Earle, K. C. Huang, and J. L. Sonnenburg, The Gut Microbiome: Connecting Spatial Organization to Function, Cell Host & Microbe, vol.21, pp.433-442, 2017.

M. Tschurtschenthaler, T. E. Adolph, J. W. Ashcroft, L. Niederreiter, R. Bharti et al., Defective ATG16L1-mediated removal of IRE1? drives Crohn's disease-like ileitis, J. Exp. Med, vol.214, pp.401-422, 2017.

S. Vaishnava, C. L. Behrendt, A. S. Ismail, L. Eckmann, and L. V. Hooper, Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface, Proc. Natl. Acad. Sci. U.S.A, vol.105, pp.20858-20863, 2008.

S. Vaishnava, M. Yamamoto, K. M. Severson, K. A. Ruhn, X. Yu et al., The antibacterial lectin RegIIIgamma promotes the spatial segregation of microbiota and host in the intestine, Science, vol.334, pp.255-258, 2011.

K. L. Vandussen and L. C. Samuelson, Mouse atonal homolog 1 directs intestinal progenitors to secretory cell rather than absorptive cell fate, Dev. Biol, vol.346, pp.215-223, 2010.

A. Vidrich, J. M. Buzan, B. Brodrick, C. Ilo, L. Bradley et al., Fibroblast growth factor receptor-3 regulates Paneth cell lineage allocation and accrual of epithelial stem cells during murine intestinal development, Am. J. Physiol. Gastrointest. Liver Physiol, vol.297, pp.168-178, 2009.

M. Vignais, A. Caicedo, J. Brondello, and C. Jorgensen, Cell Connections by Tunneling Nanotubes: Effects of Mitochondrial Trafficking on Target Cell Metabolism, Homeostasis, and Response to Therapy, Stem Cells International, vol.2017, pp.1-14, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01759757

M. A. Vinolo, H. G. Rodrigues, E. Hatanaka, C. B. Hebeda, S. H. Farsky et al., Short-chain fatty acids stimulate the migration of neutrophils to inflammatory sites, Clin. Sci, vol.117, pp.331-338, 2009.

F. E. Vuik, S. A. Nieuwenburg, M. Bardou, I. Lansdorp-vogelaar, M. Dinis-ribeiro et al., Increasing incidence of colorectal cancer in young adults in Europe over the last 25 years, Gut gutjnl, 2018.

T. Wagner, J. Wirth, J. Meyer, B. Zabel, M. Held et al., Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9, Cell, vol.79, pp.1111-1120, 1994.

B. Wang, X. Rong, E. N. Palladino, J. Wang, A. M. Fogelman et al., Phospholipid Remodeling and Cholesterol Availability Regulate Intestinal Stemness and Tumorigenesis, Cell Stem Cell, vol.22, pp.206-220, 2018.

Y. A. Wanniarachchi, P. Kaczmarek, A. Wan, and E. M. Nolan, Human defensin 5 disulfide array mutants: disulfide bond deletion attenuates antibacterial activity against Staphylococcus aureus, Biochemistry, vol.50, pp.8005-8017, 2011.

J. Wehkamp, N. H. Salzman, E. Porter, S. Nuding, M. Weichenthal et al., Reduced Paneth cell alpha-defensins in ileal Crohn's disease, Proc. Natl. Acad. Sci. U.S.A, vol.102, pp.18129-18134, 2005.

J. Wehkamp, G. Wang, I. Kübler, S. Nuding, A. Gregorieff et al., The Paneth cell alpha-defensin deficiency of ileal Crohn's disease is linked to Wnt/Tcf-4, J. Immunol, vol.179, pp.3109-3118, 2007.

P. Wei, K. K. Dove, C. Bensard, J. C. Schell, and J. Rutter, The Force Is Strong with This One: Metabolism (Over)powers Stem Cell Fate, Trends in Cell Biology, vol.28, pp.551-559, 2018.

Y. Wen, X. Xiong, T. Scott, A. T. Li, C. Wang et al., The mitochondrial retrograde signaling regulates Wnt signaling to promote tumorigenesis in colon cancer, Cell Death & Differentiation, 2019.

C. B. Westphalen, S. Asfaha, Y. Hayakawa, Y. Takemoto, D. J. Lukin et al., Long-lived intestinal tuft cells serve as colon cancer-initiating cells, J. Clin. Invest, vol.124, pp.1283-1295, 2014.

C. B. Wilen, S. Lee, L. Hsieh, R. C. Orchard, C. Desai et al., Tropism for tuft cells determines immune promotion of norovirus pathogenesis, Science, vol.360, pp.204-208, 2018.

C. L. Wilson, A. J. Ouellette, D. P. Satchell, T. Ayabe, Y. S. López-boado et al., Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense, Science, vol.286, pp.113-117, 1999.

N. Wittkopf, C. Günther, E. Martini, M. Waldner, K. U. Amann et al., Lack of intestinal epithelial atg7 affects paneth cell granule formation but does not compromise immune homeostasis in the gut, Clin. Dev. Immunol, p.278059, 2012.

J. M. Wong, R. De-souza, C. W. Kendall, A. Emam, and D. J. Jenkins, Colonic health: fermentation and short chain fatty acids, J. Clin. Gastroenterol, vol.40, pp.235-243, 2006.

J. J. Worthington, F. Reimann, and F. M. Gribble, Enteroendocrine cells-sensory sentinels of the intestinal environment and orchestrators of mucosal immunity, Mucosal Immunology, vol.11, pp.3-20, 2018.

L. Wrzosek, S. Miquel, M. Noordine, S. Bouet, M. Chevalier-curt et al., Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii influence the production of mucus glycans and the development of goblet cells in the colonic epithelium of a gnotobiotic model rodent, BMC Biol, vol.11, p.61, 2013.
URL : https://hal.archives-ouvertes.fr/hal-01001072

R. M. Xicola, Z. Manojlovic, G. J. Augustus, S. S. Kupfer, R. Emmadi et al., Lack of APC somatic mutation is associated with earlyonset colorectal cancer in African Americans, Carcinogenesis, vol.39, pp.1331-1341, 2018.

K. S. Yan, L. A. Chia, X. Li, A. Ootani, J. Su et al., The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations, Proc. Natl. Acad. Sci. U.S.A, vol.109, pp.466-471, 2012.

K. S. Yan, C. Y. Janda, J. Chang, G. X. Zheng, K. A. Larkin et al., Non-equivalence of Wnt and R-spondin ligands during Lgr5 + intestinal stemcell self-renewal, Nature, vol.545, pp.238-242, 2017.

Ö. H. Yilmaz, P. Katajisto, D. W. Lamming, Y. Gültekin, K. E. Bauer-rowe et al., mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake, Nature, vol.486, pp.490-495, 2012.

X. Yin, H. F. Farin, J. H. Van-es, H. Clevers, R. Langer et al., Niche-independent high-purity cultures of Lgr5 + intestinal stem cells and their progeny, Nature Methods, vol.11, pp.106-112, 2014.

W. Yu, X. Liu, J. Shen, O. Jovanovic, E. E. Pohl et al., Metabolic regulation by the mitochondrial phosphatase PTPMT1 is required for hematopoietic stem cell differentiation, Cell Stem Cell, vol.12, pp.62-74, 2013.

S. Yui, T. Nakamura, T. Sato, Y. Nemoto, T. Mizutani et al., Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5 + stem cell, Nat. Med, vol.18, pp.618-623, 2012.

Y. Zhang, M. A. Hoon, J. Chandrashekar, K. L. Mueller, B. Cook et al., Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways, Cell, vol.112, pp.293-301, 2003.

L. Zheng, C. J. Kelly, K. D. Battista, R. Schaefer, J. M. Lanis et al., Microbial-derived Butyrate Promotes Epithelial Barrier Function Through IL-10 Receptor-dependent Repression of Claudin-2, J Immunol, vol.199, pp.2976-2984, 2017.

Q. Zhou, B. Zhang, N. Verne, and G. , Intestinal membrane permeability and hypersensitivity in the irritable bowel syndrome, PAIN, vol.146, pp.41-46, 2009.

. Le-maintien-de-l'homéostasie-intestinale, Sox9 est requis pour la régulation du destin cellulaire des CSI, c'est à dire l'équilibre entre l'auto-renouvellement des CSI et leur différenciation cellulaire. Les mécanismes régulés par Sox9 mettent en jeu le métabolisme cellulaire, un acteur clé du destin des cellules souches. Nos travaux montrent également que le maintien d'une niche intacte est nécessaire au contrôle du devenir des CSI. La délétion de Sox9 altère l'intégrité mitochondriale et favorise la production de ROS mitochondriaux qui pourrait moduler le destin des CSI vers un état différencié. En parallèle, nous avons mis en évidence que l'invalidation de Sox9 après l'acquisition d'un événement initiateur tel que la perte de fonction du gène suppresseur de tumeur Apc, affecte de façon majeure le destin des CSC vers un état souche ainsi que leur métabolisme cellulaire, Les CSI assurent le renouvellement et la régénération de l'intestin en cas de lésions mais elles peuvent être également à l'origine des tumeurs intestinales. Le facteur de transcription Sox9 est un candidat intéressant comme régulateur clé de l'homéostasie intestinale car il est exprimé dans les CSI, les cellules de Paneth et les cellules tuft. De plus