Diversification of multipotential postmitotic mouse retinal ganglion cell precursors into discrete types
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 non-overlapping 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.
Sequencing data has been submitted under GSE185671. Reviewer token : evchicgutpqpnoj.Computational scripts are available at : https://github.com/shekharlab/mouseRGCdev
Diversification of multipotential postmitotic mouse retinal ganglion cell precursors into discrete typesNCBI Gene Expression Omnibus, GSE19373.
Article and author information
National Institutes of Health (R37NS029169)
- Joshua R Sanes
National Institutes of Health (R01EY022073)
- Joshua R Sanes
National Institutes of Health (R00EY028625)
- Karthik Shekhar
National Science Foundation (GRP DGE1752814)
- Salwan Butrus
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All animal experiments were approved by the Institutional Animal Care and Use Committees (IACUC) at Harvard University. Mice were maintained in pathogen-free facilities under standard housing conditions with continuous access to food and water. Animals used in this study include both males and females. A meta-analysis (not shown) did not show any systematic sex-related effects in either differentially expressed genes or cell-type proportions.
- Carol A Mason, Columbia University, United States
- Received: September 11, 2021
- Preprint posted: October 21, 2021 (view preprint)
- Accepted: February 21, 2022
- Accepted Manuscript published: February 22, 2022 (version 1)
- Version of Record published: March 25, 2022 (version 2)
© 2022, Shekhar et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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