Diversification of multipotential postmitotic mouse retinal ganglion cell precursors into discrete types
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Abstract
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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The development of a cell type may not follow a simple trajectory but involves multiple steps of divergent or convergent differentiation.
“The development of a cell type may not follow a simple trajectory but involves multiple steps of divergent or convergent differentiation (Shekhar et al., 2022), the former due to the multipotency of progenitors or transitional cell types and the latter due to convergence of different transitional types.”
From What is a cell type and how to define it? (2022) · cites this paper as Shekhar et al., 2022
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Intrinsic and Induced Neuronal Regeneration in the Mammalian Retina
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Targeting pioneer transcription factor Ascl1 to promote optic nerve regenerationPreprint
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(2022) · Society for Neuroscience eBooks · doi:10.1523/hon.012011
Competent to Stand Trial—The Case for Temporal Control of Retinal Development
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Retinal Lineages: One Cell at a Time
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Protocadherin 9 promotes cell survival of different bipolar subtypes in the developing mouse retinaPreprint
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Morphological Comparison of Human Midgestational and Mouse Postnatal Retinal Development
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The Onset of Breathing at Birth Switches Off Regenerative CapacityPreprint
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- Authors
- Shekhar, K., Whitney, I. E., Butrus, S., Peng, Y.-R., & Sanes, J. R.
- Affiliations
- QB3 (US)
- Harvard University (US)
- Corresponding author
- Shekhar, Karthik
- Sanes, Joshua R
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2022-02-22
- Volume
- 11
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC8956290
- OpenAlex
- W4225688952
- Cited by
- 68
- References
- 98
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 17 · 2023: 16 · 2022: 11
- FWCI
- 5.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Funders
- National Institutes of Health (R37NS029169, R01EY022073, R00EY028625)
- National Science Foundation (GRP DGE1752814)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- retinal ganglion cells, single-cell transcriptomics, transcription factors, ipsilateral and contralateral projections, retinal development, mouse retina
- MeSH terms
- Animals, Mice, Transgenic, Retina, Retinal Ganglion Cells, Transcription Factors, Mice
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