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Caractérisation des premières étapes de différenciation des cellules hématopoïétiques à l'échelle de la cellule unique

Abstract : Despite intensively studies, the fundamental mechanisms of cell fate decision during cellular differentiation still remain unclear. The deterministic mechanisms, often based on studies of large cell populations, cannot explain the difference between individual cell fates choices placed in the same environment. The aim of my thesis work is to study the first steps of hematopoietic cell differentiation at the single cell level thanks to transcriptomic, proteomic and morphological analyses. Two differentiation models have been used: T regulatory lymphocytes and human cord blood-derived CD34+ cells. The behavior of individual cells following stimulation has been analyzed. Using time-lapse microscopy coupled to single cell molecular analyses, we could demonstrate that the cell fate choice is not a unique, programmed event. First, the cell reaches a metastable “multi-primed” state, which is characterized by a mixed lineage gene expression pattern. After transition through an “uncertain”, unstable state, characterized by fluctuations between two phenotypes, the cell reaches a stable state. Our observations are coherent with a stochastic model of cell fate decision. The differentiation is likely to be a spontaneous, dynamic, fluctuating and not a deterministic process. The cell fate decisions are taken by individual cells.
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Submitted on : Tuesday, April 23, 2019 - 11:12:14 AM
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Alice Moussy. Caractérisation des premières étapes de différenciation des cellules hématopoïétiques à l'échelle de la cellule unique. Biologie cellulaire. Université Paris sciences et lettres, 2017. Français. ⟨NNT : 2017PSLEP029⟩. ⟨tel-02106673⟩

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