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Publication : Key transcription factors influence the epigenetic landscape to regulate retinal cell differentiation.

First Author  Ge Y Year  2023
Journal  Nucleic Acids Res Volume  51
Issue  5 Pages  2151-2176
PubMed ID  36715342 Mgi Jnum  J:334110
Mgi Id  MGI:7445907 Doi  10.1093/nar/gkad026
Citation  Ge Y, et al. (2023) Key transcription factors influence the epigenetic landscape to regulate retinal cell differentiation. Nucleic Acids Res 51(5):2151-2176
abstractText  How the diverse neural cell types emerge from multipotent neural progenitor cells during central nervous system development remains poorly understood. Recent scRNA-seq studies have delineated the developmental trajectories of individual neural cell types in many neural systems including the neural retina. Further understanding of the formation of neural cell diversity requires knowledge about how the epigenetic landscape shifts along individual cell lineages and how key transcription factors regulate these changes. In this study, we dissect the changes in the epigenetic landscape during early retinal cell differentiation by scATAC-seq and identify globally the enhancers, enriched motifs, and potential interacting transcription factors underlying the cell state/type specific gene expression in individual lineages. Using CUT&Tag, we further identify the enhancers bound directly by four key transcription factors, Otx2, Atoh7, Pou4f2 and Isl1, including those dependent on Atoh7, and uncover the sequential and combinatorial interactions of these factors with the epigenetic landscape to control gene expression along individual retinal cell lineages such as retinal ganglion cells (RGCs). Our results reveal a general paradigm in which transcription factors collaborate and compete to regulate the emergence of distinct retinal cell types such as RGCs from multipotent retinal progenitor cells (RPCs).
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