Journal
ELIFE
Volume 11, Issue -, Pages -Publisher
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.73809
Keywords
retinal ganglion cells; single-cell RNA-seq; cell type diversification; optimal transport; Mouse
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Funding
- National Institutes of Health [R37NS029169, R01EY022073, R00EY028625]
- National Science Foundation [GRP DGE1752814]
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This study investigates how mouse retinal ganglion cell precursors diversify from a single type into multiple discrete types using single-cell RNA-seq. The findings suggest that the transcriptomic type identity of RGC precursors is not specified at mitotic exit but acquired gradually, and some types can only be identified a week after they are generated.
The genesis of broad neuronal classes from multipotential neural progenitor cells has been extensively studied, but less is known about the diversification of a single neuronal class into multiple types. We used single-cell RNA-seq to study how newly born (postmitotic) mouse retinal ganglion cell (RGC) precursors diversify into ~45 discrete types. Computational analysis provides evidence that RGC transcriptomic type identity is not specified at mitotic exit, but acquired by gradual, asynchronous restriction of postmitotic multipotential precursors. Some types are not identifiable until a week after they are generated. Immature RGCs may be specified to project ipsilaterally or contralaterally to the rest of the brain before their type identity emerges. Optimal transport inference identifies groups of RGC precursors with largely nonoverlapping fates, distinguished by selectively expressed transcription factors that could act as fate determinants. Our study provides a framework for investigating the molecular diversification of discrete types within a neuronal class.
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