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Reconstruction of gene regulatory networks defining the cell fate transition processes

Abstract : The cell fate acquisition is a highly complex phenomenon that involves a plethora of intrinsic and extrinsic instructive signals. However, despite the important progress in identification of key regulatory factors of this process, the mechanistic links between transcription factors, epigenome and chromatin structure which coordinate the regulation of cell differentiation and deregulation of gene networks during cell transformation are largely unknown. To address these questions for two model systems of cell fate transitions, namely the neuronal and endodermal cell differentiation induced by the morphogen retinoic acid and the stepwise tumorigenesis of primary human cells, we conducted integrative transcriptome, epigenome and chromatin architecture studies. Through extensive integration with thousands of available genomic data sets, we deciphered the gene regulatory networks of these processes and revealed new insights in the molecular circuitry of cell fate acquisition. The understanding of regulatory mechanisms that underlie the cell fate decision processes not only brings the fundamental understanding of cause-and-consequence relationships inside the cell, but also open the doors to the directed trans-differentiation.
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Submitted on : Thursday, March 8, 2018 - 4:47:04 PM
Last modification on : Friday, October 23, 2020 - 4:36:58 PM
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  • HAL Id : tel-01726970, version 1



Valeriya Malysheva. Reconstruction of gene regulatory networks defining the cell fate transition processes. Genomics [q-bio.GN]. Université de Strasbourg, 2016. English. ⟨NNT : 2016STRAJ084⟩. ⟨tel-01726970⟩



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