Two transcription factors, Pou4f2 and Isl1, are sufficient to specify the retinal ganglion cell fate
Fuguo Wu,Fuguo Wu,Tadeusz J. Kaczynski,Santhosh Sethuramanujam,Renzhong Li,Renzhong Li,Varsha Jain,Malcolm M. Slaughter,Malcolm M. Slaughter,Xiuqian Mu +9 more
TLDR
It is reported that ectopic expression of Pou4f2 and Isl1 in the Atoh7-null retina using a binary knockin-transgenic system is sufficient for the specification of the RGC fate.Abstract:
As with other retinal cell types, retinal ganglion cells (RGCs) arise from multipotent retinal progenitor cells (RPCs), and their formation is regulated by a hierarchical gene-regulatory network (GRN). Within this GRN, three transcription factors—atonal homolog 7 (Atoh7), POU domain, class 4, transcription factor 2 (Pou4f2), and insulin gene enhancer protein 1 (Isl1)—occupy key node positions at two different stages of RGC development. Atoh7 is upstream and is required for RPCs to gain competence for an RGC fate, whereas Pou4f2 and Isl1 are downstream and regulate RGC differentiation. However, the genetic and molecular basis for the specification of the RGC fate, a key step in RGC development, remains unclear. Here we report that ectopic expression of Pou4f2 and Isl1 in the Atoh7-null retina using a binary knockin-transgenic system is sufficient for the specification of the RGC fate. The RGCs thus formed are largely normal in gene expression, survive to postnatal stages, and are physiologically functional. Our results indicate that Pou4f2 and Isl1 compose a minimally sufficient regulatory core for the RGC fate. We further conclude that during development a core group of limited transcription factors, including Pou4f2 and Isl1, function downstream of Atoh7 to determine the RGC fate and initiate RGC differentiation.read more
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Journal ArticleDOI
A human cell atlas of fetal gene expression
Junyue Cao,Diana R. O’Day,Hannah A. Pliner,Paul D. Kingsley,Mei Deng,Riza M. Daza,Michael Zager,Kimberly A. Aldinger,Kimberly A. Aldinger,Ronnie Blecher-Gonen,Fan Zhang,Malte Spielmann,Malte Spielmann,James Palis,Dan Doherty,Dan Doherty,Frank J. Steemers,Ian A. Glass,Ian A. Glass,Cole Trapnell,Jay Shendure +20 more
TL;DR: A pooled approach using three levels of combinatorial indexing to examine the single-cell gene expression and chromatin landscapes from 15 organs in fetal samples, which generates comprehensive atlases of early human development.
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Yang Jiang,Yang Jiang,Jinpeng Zhou,Junshuang Zhao,Haiying Zhang,Long Li,Hao Li,Lian Chen,Jiangfeng Hu,Wei Zheng,Zhitao Jing +10 more
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Eye organogenesis: A hierarchical view of ocular development.
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