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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 (R...

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Autores principales: Shekhar, Karthik, Whitney, Irene E, Butrus, Salwan, Peng, Yi-Rong, Sanes, Joshua R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8956290/
https://www.ncbi.nlm.nih.gov/pubmed/35191836
http://dx.doi.org/10.7554/eLife.73809
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author Shekhar, Karthik
Whitney, Irene E
Butrus, Salwan
Peng, Yi-Rong
Sanes, Joshua R
author_facet Shekhar, Karthik
Whitney, Irene E
Butrus, Salwan
Peng, Yi-Rong
Sanes, Joshua R
author_sort Shekhar, Karthik
collection PubMed
description 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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spelling pubmed-89562902022-03-26 Diversification of multipotential postmitotic mouse retinal ganglion cell precursors into discrete types Shekhar, Karthik Whitney, Irene E Butrus, Salwan Peng, Yi-Rong Sanes, Joshua R eLife Developmental Biology 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. eLife Sciences Publications, Ltd 2022-02-22 /pmc/articles/PMC8956290/ /pubmed/35191836 http://dx.doi.org/10.7554/eLife.73809 Text en © 2022, Shekhar et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology
Shekhar, Karthik
Whitney, Irene E
Butrus, Salwan
Peng, Yi-Rong
Sanes, Joshua R
Diversification of multipotential postmitotic mouse retinal ganglion cell precursors into discrete types
title Diversification of multipotential postmitotic mouse retinal ganglion cell precursors into discrete types
title_full Diversification of multipotential postmitotic mouse retinal ganglion cell precursors into discrete types
title_fullStr Diversification of multipotential postmitotic mouse retinal ganglion cell precursors into discrete types
title_full_unstemmed Diversification of multipotential postmitotic mouse retinal ganglion cell precursors into discrete types
title_short Diversification of multipotential postmitotic mouse retinal ganglion cell precursors into discrete types
title_sort diversification of multipotential postmitotic mouse retinal ganglion cell precursors into discrete types
topic Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8956290/
https://www.ncbi.nlm.nih.gov/pubmed/35191836
http://dx.doi.org/10.7554/eLife.73809
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