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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/73809 |
| _version_ | 1811200583196999680 |
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| author | Karthik Shekhar Irene E Whitney Salwan Butrus Yi-Rong Peng Joshua R Sanes |
| author_facet | Karthik Shekhar Irene E Whitney Salwan Butrus Yi-Rong Peng Joshua R Sanes |
| author_sort | Karthik Shekhar |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T02:05:57Z |
| format | Article |
| id | doaj.art-a10efda4c53b4e888c1b7ce1e26c7c78 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:05:57Z |
| publishDate | 2022-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-a10efda4c53b4e888c1b7ce1e26c7c782022-12-22T03:52:32ZengeLife Sciences Publications LtdeLife2050-084X2022-02-011110.7554/eLife.73809Diversification of multipotential postmitotic mouse retinal ganglion cell precursors into discrete typesKarthik Shekhar0https://orcid.org/0000-0003-4349-6600Irene E Whitney1Salwan Butrus2Yi-Rong Peng3Joshua R Sanes4https://orcid.org/0000-0001-8926-8836Department of Chemical and Biomolecular Engineering; Helen Wills Neuroscience Institute; Center for Computational Biology; California Institute for Quantitative Biosciences, QB3, University of California, Berkeley, Berkeley, United States; Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, United States; Broad Institute of Harvard and MIT, Cambridge, United States; Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, United StatesCenter for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, United StatesDepartment of Chemical and Biomolecular Engineering; Helen Wills Neuroscience Institute; Center for Computational Biology; California Institute for Quantitative Biosciences, QB3, University of California, Berkeley, Berkeley, United StatesCenter for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States; Department of Ophthalmology, Stein Eye Institute, UCLA David Geffen School of Medicine, Los Angeles, United StatesCenter for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, United StatesThe 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.https://elifesciences.org/articles/73809retinal ganglion cellssingle-cell RNA-seqcell type diversificationoptimal transport |
| spellingShingle | Karthik Shekhar Irene E Whitney Salwan Butrus Yi-Rong Peng Joshua R Sanes Diversification of multipotential postmitotic mouse retinal ganglion cell precursors into discrete types eLife retinal ganglion cells single-cell RNA-seq cell type diversification optimal transport |
| 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 | retinal ganglion cells single-cell RNA-seq cell type diversification optimal transport |
| url | https://elifesciences.org/articles/73809 |
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