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Diversification of multipotential postmitotic mouse retinal ganglion cell precursors into discrete types

View ORCID ProfileKarthik Shekhar, Irene E. Whitney, Salwan Butrus, Yi-Rong Peng, View ORCID ProfileJoshua R. Sanes
doi: https://doi.org/10.1101/2021.10.21.465277
Karthik Shekhar
1Department of Chemical and Biomolecular Engineering; Helen Wills Neuroscience Institute; Center for Computational Biology; California Institute for Quantitative Biosciences, QB3, University of California, Berkeley, CA, USA 94720
2Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA USA 94720
3Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
4Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge MA, 02138
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  • For correspondence: kshekhar@berkeley.edu sanesj@mcb.harvard.edu
Irene E. Whitney
4Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge MA, 02138
5Honeycomb Biotechnologies 940 Winter Street Waltham MA 02451
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Salwan Butrus
1Department of Chemical and Biomolecular Engineering; Helen Wills Neuroscience Institute; Center for Computational Biology; California Institute for Quantitative Biosciences, QB3, University of California, Berkeley, CA, USA 94720
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Yi-Rong Peng
4Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge MA, 02138
6Department of Ophthalmology, Stein Eye Institute, UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USA
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Joshua R. Sanes
4Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge MA, 02138
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  • ORCID record for Joshua R. Sanes
  • For correspondence: kshekhar@berkeley.edu sanesj@mcb.harvard.edu
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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 type identity is not specified at mitotic exit, but acquired by gradual, asynchronous fate 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 has been determined. 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.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted October 21, 2021.
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Diversification of multipotential postmitotic mouse retinal ganglion cell precursors into discrete types
Karthik Shekhar, Irene E. Whitney, Salwan Butrus, Yi-Rong Peng, Joshua R. Sanes
bioRxiv 2021.10.21.465277; doi: https://doi.org/10.1101/2021.10.21.465277
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Diversification of multipotential postmitotic mouse retinal ganglion cell precursors into discrete types
Karthik Shekhar, Irene E. Whitney, Salwan Butrus, Yi-Rong Peng, Joshua R. Sanes
bioRxiv 2021.10.21.465277; doi: https://doi.org/10.1101/2021.10.21.465277

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