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Caractérisation de la voie de signalisation NODAL lors de la différenciation des cellules souches embryonnaires

Abstract : During the development of an organism, cells differentiate and tissues self-organize spatially to form a complete living being. These phenomena are controlled by chemical signals called "morphogens" which are diffusible molecules, secreted in the extracellular medium and able to influence the differentiation of a cell. It has been shown that different concentrations of morphogen can induce different cellular identity and that the concentration of morphogen in a tissue is not spatially homogeneous. To understand how a developing tissue is organized, it is therefore necessary to know how differentiating cells decode information carried by morphogens. Among these morphogens, Nodal morphogen is of particular interest, Nodal is an important factor in the early development of the embryo, since it is involved in the specification of cell identity in embryonic and extraembryonic lineages. As it is difficult to study in an embryo quantitatively, the influence of the temporal profile of a morphogen stimulation on differentiation, we have chosen as a model system the mouse embryonic stem cells (mESC). The aim of this work was to study the influence of the temporal stimulation of different morphogens on the expression of the "Nodal" locus and on the differentiation of stem cells. To control the temporal profile of the morphogen concentration sent to cells, we use an automated microfluidic cell culture chip that allows us to observe individual cell responses in real time with the fluorescence microscope. This tool allows us to directly measure the dynamics of Nodal gene expression through different mESC lines modified to express fluorescent reporters of Nodal expression. This work made it possible to put forward an unprecedented NODAL profile out of pluripotency and a strong influence of stimulation time on the activity of the Nodal signaling pathway and on differentiation. This work is also a first step towards demonstrating the influence of cell density on the expression of the Nodal gene, but also on cell differentiation in vitro.
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Submitted on : Wednesday, October 27, 2021 - 9:34:12 AM
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Fabien Furfaro. Caractérisation de la voie de signalisation NODAL lors de la différenciation des cellules souches embryonnaires. Médecine humaine et pathologie. Université Paris Cité, 2019. Français. ⟨NNT : 2019UNIP7198⟩. ⟨tel-03405136⟩

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