Single cell transcriptomics reveals lineage trajectory of retinal ganglion cells in wild-type and Atoh7-null retinas

Fuguo Wu, Jonathan E. Bard, Julien Kann, Donald Yergeau, Darshan Sapkota, Yichen Ge, Zihua Hu, Jie Wang, Tao Liu and Xiuqian Mu ()
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Fuguo Wu: University at Buffalo
Jonathan E. Bard: University at Buffalo
Julien Kann: University at Buffalo
Donald Yergeau: University at Buffalo
Darshan Sapkota: University at Buffalo
Yichen Ge: University at Buffalo
Zihua Hu: University at Buffalo
Jie Wang: Roswell Park Comprehensive Cancer Center
Tao Liu: Roswell Park Comprehensive Cancer Center
Xiuqian Mu: University at Buffalo

Nature Communications, 2021, vol. 12, issue 1, 1-20

Abstract: Abstract Atoh7 has been believed to be essential for establishing the retinal ganglion cell (RGC) lineage, and Pou4f2 and Isl1 are known to regulate RGC specification and differentiation. Here we report our further study of the roles of these transcription factors. Using bulk RNA-seq, we identify genes regulated by the three transcription factors, which expand our understanding of the scope of downstream events. Using scRNA-seq on wild-type and mutant retinal cells, we reveal a transitional cell state of retinal progenitor cells (RPCs) co-marked by Atoh7 and other genes for different lineages and shared by all early retinal lineages. We further discover the unexpected emergence of the RGC lineage in the absence of Atoh7. We conclude that competence of RPCs for different retinal fates is defined by lineage-specific genes co-expressed in the transitional state and that Atoh7 defines the RGC competence and collaborates with other factors to shepherd transitional RPCs to the RGC lineage.

Date: 2021
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DOI: 10.1038/s41467-021-21704-4

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