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Analyse histologique et fonctionnelle du développement de précurseurs neuraux dérivés de cellules souches pluripotentes induites humaines greffés dans le cortex de la souris

Abstract : Neurodevelopmental abnormalities underlie psychiatric diseases such as schizophrenia or autism, among others. However, the genetic heterogeneity of human beings makes it difficult to establish a link between a given genome and development programs that can lead to a disease. To address this problem, induced pluripotent stem cells (iPSCs) are an ethical and effective tool. They are able to develop and differentiate into functional neurons, using a mechanism similar to in vivo development. I studied a model enabling the integration and migration of neural precursors from human iPSCs into the mouse cortex. By labelling the cells grafted by immunofluorescence, I was able to show that they differentiate mainly into upper layer cortical neurons. I have studied the relationship between host and grafted cells , and show that mouse cells participate in the development of the graft, providing vascularization, and myelinating developing human neurons. Finally, I followed the functional development of human neurons using a cell line expressing a calcium indicator, GCaMP6f, and chronically observing injected mice under a 2-photon microscope. This activity changes over time, and reflects a prenatal human brain. This model offers new possibilities for in vivo modelling of human cortical development, particularly in the study of the impact of genetic alterations in the context of psychiatric diseases.
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Submitted on : Sunday, September 26, 2021 - 1:02:08 AM
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Célia Raïs. Analyse histologique et fonctionnelle du développement de précurseurs neuraux dérivés de cellules souches pluripotentes induites humaines greffés dans le cortex de la souris. Neurosciences [q-bio.NC]. Sorbonne Université, 2019. Français. ⟨NNT : 2019SORUS333⟩. ⟨tel-03354716⟩

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