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

Cell Reports

Timothy J. Cherry¹  Jiang Qian²  Eric D. Thomas³  Andrew E. Timms³  Seth Blackshaw³  Brian S. Clark⁴  Ariel E. Telger⁴  Pin Lyu⁵  Megan Gimmen⁶  Thanh Hoang⁶  Siqi Chen⁶  Nguyet Le⁶  Clayton P. Santiago⁶  Lizhi Jiang⁶  Kurt Weir⁶  Dong Won Kim⁶  David F. Espinoza⁶  Haley Appel⁶ 

[1] Brotman Baty Institute, Seattle, WA 98195, USA;Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA;Center for Developmental Biology and Regenerative Medicine, Seattle Children’s Research Institute, Seattle, WA 98101, USA;Department of Ophthalmology and Visual Sciences, Brotman Baty Institute, Seattle, WA 98195, USA;Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;

关键词: retina;    development;    transcription factor;    neurogenesis;    single-cell ATAC-seq;    single-cell RNA-seq;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: 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.

【 授权许可】

Unknown