@article{d62ec722cd30465eae4b0c307d06b7bc,
title = "Gene regulatory networks controlling temporal patterning, neurogenesis, and cell-fate specification in mammalian retina",
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.",
keywords = "NFI, development, gene regulatory network, neurogenesis, progenitor, retina, single-cell ATAC-seq, single-cell RNA-seq, temporal patterning, transcription factor",
author = "Pin Lyu and Thanh Hoang and Santiago, {Clayton P.} and Thomas, {Eric D.} and Timms, {Andrew E.} and Haley Appel and Megan Gimmen and Nguyet Le and Lizhi Jiang and Kim, {Dong Won} and Siqi Chen and Espinoza, {David F.} and Telger, {Ariel E.} and Kurt Weir and Clark, {Brian S.} and Cherry, {Timothy J.} and Jiang Qian and Seth Blackshaw",
note = "Funding Information: The authors would like to thank Richard Gronostajski for providing Nfia/b/x conditional mice, Linda Orzolek and Tyler Creamer at the Hopkins Transcriptomics and Deep Sequencing Core for use of the 10× Genomics Chromium controller and library sequencing, and J. Nathans, H. Jaspers, M. Cayouette, A. Javed, L. Goff, J. Kebschull, W. Yap, and members of the Blackshaw lab for comments on the manuscript. This work was supported by the NIH National Eye Institute grants R01EY020560 and U01EY027267 to S.B., EY001765 in support of flow sorting, R01EY029548 and P30EY001765 to J.Q., R00EY027844 to B.S.C., R01EY028584 to T.J.C., P30 EY002687 in support of confocal imaging, and 2T32EY007143 to C.P.S. S.B. is supported by a Stein Innovation Award from Research to Prevent Blindness . T.J.C. is supported by a grant from the Lowy Medical Research Institute , and B.S.C. is supported by an unrestricted grant to the Washington University Department of Ophthalmology and Visual Sciences and a Career Development Award from Research to Prevent Blindness . Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = nov,
day = "16",
doi = "10.1016/j.celrep.2021.109994",
language = "English",
volume = "37",
journal = "Cell Reports",
issn = "2211-1247",
number = "7",
}