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Cross-species transcriptomic and epigenomic analysis reveals key regulators of injury response and neuronal regeneration in vertebrate retinas

Thanh Hoang, Jie Wang, Patrick Boyd, Fang Wang, Clayton Santiago, Lizhi Jiang, Manuela Lahne, Levi J. Todd, Cristian Saez, Sooyeon Yoo, Casey Keuthan, Isabella Palazzo, Natalie Squires, Warren A. Campbell, Meng Jia, Fatemeh Rajaii, Trisha Payail, Guohua Wang, John Ash, Andy J. Fischer, David R. Hyde, Jiang Qian, View ORCID ProfileSeth Blackshaw
doi: https://doi.org/10.1101/717876
Thanh Hoang
1Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
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Jie Wang
2Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
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Patrick Boyd
7Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, 46556 USA
8Center for Stem Cells and Regenerative Medicine, University of Notre Dame, Notre Dame, IN, 46556 USA
9Center for Zebrafish Research, University of Notre Dame, Notre Dame, IN, 46556 USA
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Fang Wang
2Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
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Clayton Santiago
1Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
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Lizhi Jiang
1Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
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Manuela Lahne
7Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, 46556 USA
8Center for Stem Cells and Regenerative Medicine, University of Notre Dame, Notre Dame, IN, 46556 USA
9Center for Zebrafish Research, University of Notre Dame, Notre Dame, IN, 46556 USA
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Levi J. Todd
10Department of Neuroscience, Ohio State University Wexner Medical Center, Columbus, OH, 43210 USA
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Cristian Saez
1Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
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Sooyeon Yoo
1Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
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Casey Keuthan
11Department of Ophthalmology, University of Florida School of Medicine, Gainesville, FL, 32610 USA
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Isabella Palazzo
10Department of Neuroscience, Ohio State University Wexner Medical Center, Columbus, OH, 43210 USA
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Natalie Squires
11Department of Ophthalmology, University of Florida School of Medicine, Gainesville, FL, 32610 USA
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Warren A. Campbell
11Department of Ophthalmology, University of Florida School of Medicine, Gainesville, FL, 32610 USA
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Meng Jia
7Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, 46556 USA
8Center for Stem Cells and Regenerative Medicine, University of Notre Dame, Notre Dame, IN, 46556 USA
9Center for Zebrafish Research, University of Notre Dame, Notre Dame, IN, 46556 USA
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Fatemeh Rajaii
2Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
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Trisha Payail
2Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
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Guohua Wang
2Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
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John Ash
11Department of Ophthalmology, University of Florida School of Medicine, Gainesville, FL, 32610 USA
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Andy J. Fischer
10Department of Neuroscience, Ohio State University Wexner Medical Center, Columbus, OH, 43210 USA
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David R. Hyde
7Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, 46556 USA
8Center for Stem Cells and Regenerative Medicine, University of Notre Dame, Notre Dame, IN, 46556 USA
9Center for Zebrafish Research, University of Notre Dame, Notre Dame, IN, 46556 USA
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  • For correspondence: dhyde@nd.edu jiang.qian@jhmi.edu sblack@jhmi.edu
Jiang Qian
2Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
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  • For correspondence: dhyde@nd.edu jiang.qian@jhmi.edu sblack@jhmi.edu
Seth Blackshaw
1Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
2Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
3Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
4Center for Human Systems Biology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
6Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
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  • ORCID record for Seth Blackshaw
  • For correspondence: dhyde@nd.edu jiang.qian@jhmi.edu sblack@jhmi.edu
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Abstract

Injury induces retinal Müller glia of cold-blooded, but not mammalian, vertebrates to generate neurons. To identify gene regulatory networks that control neuronal reprogramming in retinal glia, we comprehensively profiled injury-dependent changes in gene expression and chromatin conformation in Müller glia from zebrafish, chick and mice using bulk RNA and ATAC-Seq, as well as single-cell RNA-Seq. Cross-species integrative analysis of these data, together with functional validation of candidate genes, identified evolutionarily conserved and species-specific gene networks controlling glial quiescence, gliosis and neurogenesis. In zebrafish and chick, transition from quiescence to gliosis is a critical stage in acquisition of neurogenic competence, while in mice a dedicated network suppresses this transition and rapidly restores quiescence. Selective disruption of NFI family transcription factors, which maintain and restore quiescence, enables Müller glia to proliferate and robustly generate neurons in adult mice after retinal injury. These comprehensive resources and findings will facilitate the design of cell-based therapies aimed at restoring retinal neurons lost to degenerative disease.

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Posted July 31, 2019.
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Cross-species transcriptomic and epigenomic analysis reveals key regulators of injury response and neuronal regeneration in vertebrate retinas
Thanh Hoang, Jie Wang, Patrick Boyd, Fang Wang, Clayton Santiago, Lizhi Jiang, Manuela Lahne, Levi J. Todd, Cristian Saez, Sooyeon Yoo, Casey Keuthan, Isabella Palazzo, Natalie Squires, Warren A. Campbell, Meng Jia, Fatemeh Rajaii, Trisha Payail, Guohua Wang, John Ash, Andy J. Fischer, David R. Hyde, Jiang Qian, Seth Blackshaw
bioRxiv 717876; doi: https://doi.org/10.1101/717876
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Cross-species transcriptomic and epigenomic analysis reveals key regulators of injury response and neuronal regeneration in vertebrate retinas
Thanh Hoang, Jie Wang, Patrick Boyd, Fang Wang, Clayton Santiago, Lizhi Jiang, Manuela Lahne, Levi J. Todd, Cristian Saez, Sooyeon Yoo, Casey Keuthan, Isabella Palazzo, Natalie Squires, Warren A. Campbell, Meng Jia, Fatemeh Rajaii, Trisha Payail, Guohua Wang, John Ash, Andy J. Fischer, David R. Hyde, Jiang Qian, Seth Blackshaw
bioRxiv 717876; doi: https://doi.org/10.1101/717876

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