Gene regulatory networks controlling temporal patterning, neurogenesis, and cell-fate specification in mammalian retina

Pin Lyu, Thanh Hoang, Clayton P. Santiago, Eric D. Thomas, Andrew E. Timms, Haley Appel, Megan Gimmen, Nguyet Le, Lizhi Jiang, Dong Won Kim, Siqi Chen, David F. Espinoza, Ariel E. Telger, Kurt Weir, Brian S. Clark, Timothy J. Cherry, Jiang Qian, Seth Blackshaw

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Gene regulatory networks (GRNs), consisting of transcription factors and their target sites, control neurogenesis and cell-fate specification in the developing central nervous system. In this study, we use integrated single-cell RNA and single-cell ATAC sequencing (scATAC-seq) analysis in developing mouse and human retina to identify multiple interconnected, evolutionarily conserved GRNs composed of cell-type-specific transcription factors that both activate genes within their own network and inhibit genes in other networks. These GRNs control temporal patterning in primary progenitors, regulate transition from primary to neurogenic progenitors, and drive specification of each major retinal cell type. We confirm that NFI transcription factors selectively activate expression of genes promoting late-stage temporal identity in primary retinal progenitors and identify other transcription factors that regulate rod photoreceptor specification in postnatal retina. This study inventories cis- and trans-acting factors that control retinal development and can guide cell-based therapies aimed at replacing retinal neurons lost to disease.

Original languageEnglish
Article number109994
JournalCell Reports
Volume37
Issue number7
DOIs
StatePublished - Nov 16 2021

Keywords

  • NFI
  • development
  • gene regulatory network
  • neurogenesis
  • progenitor
  • retina
  • single-cell ATAC-seq
  • single-cell RNA-seq
  • temporal patterning
  • transcription factor

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