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Deciphering changes in cellular identity during development, reprogramming and oncogenesis

Abstract : In the classical view of development, changes of cellular identity take place only during differentiation. In this process, the pluripotent stem cell, a cell capable of forming the whole organism, differentiates ultimately in specified somatic cells. This differentiation is always accompanied by an increasing loss of cellular plasticity, which is the ability to give rise to multiple cell type, and acquisition of specific features and characteristics typical of the new cell. New advances in the developmental biology proved this wrong, showing that cells more advanced in the developmental path can revert to less differentiated states. Already in the pluripotent compartment of the embryo, cells more committed can go back to more naïve states, and the processes are convertible, showing the plasticity of the differentiation process. During my PhD, I identified the ligand Netrin-1 and its receptors Neo-1 and Unc5-b as novel regulators of naïve states. Moreover, a differentiated somatic cell can reacquire cellular plasticity and revert to the pluripotent state, giving rise to induced pluripotent stem cells (iPSCs), or, in a pathological context, the reacquisition of plasticity can anticipate the malignant transformation and cancer formation. As a second project of my PhD, I identified the axis c-Myc/Atoh8/Wnt as a pathway orchestrating iPSCs generation and malignant transformation
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https://tel.archives-ouvertes.fr/tel-02500727
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Giacomo Furlan. Deciphering changes in cellular identity during development, reprogramming and oncogenesis. Cancer. Université de Lyon, 2019. English. ⟨NNT : 2019LYSE1309⟩. ⟨tel-02500727⟩

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