Single-Cell Profiles of Retinal Ganglion Cells Differing in Resilience to Injury Reveal Neuroprotective Genes
© 2019 Elsevier Inc. Neuronal types in the central nervous system differ dramatically in their resilience to injury or other insults. Here we studied the selective resilience of mouse retinal ganglion cells (RGCs) following optic nerve crush (ONC), which severs their axons and leads to death of ∼80%...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier BV
2021
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| Online Access: | https://hdl.handle.net/1721.1/136567 |
| _version_ | 1826194426431537152 |
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| author | Tran, Nicholas M Shekhar, Karthik Whitney, Irene E Jacobi, Anne Benhar, Inbal Hong, Guosong Yan, Wenjun Adiconis, Xian Arnold, McKinzie E Lee, Jung Min Levin, Joshua Z Lin, Dingchang Wang, Chen Lieber, Charles M Regev, Aviv He, Zhigang Sanes, Joshua R |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Tran, Nicholas M Shekhar, Karthik Whitney, Irene E Jacobi, Anne Benhar, Inbal Hong, Guosong Yan, Wenjun Adiconis, Xian Arnold, McKinzie E Lee, Jung Min Levin, Joshua Z Lin, Dingchang Wang, Chen Lieber, Charles M Regev, Aviv He, Zhigang Sanes, Joshua R |
| author_sort | Tran, Nicholas M |
| collection | MIT |
| description | © 2019 Elsevier Inc. Neuronal types in the central nervous system differ dramatically in their resilience to injury or other insults. Here we studied the selective resilience of mouse retinal ganglion cells (RGCs) following optic nerve crush (ONC), which severs their axons and leads to death of ∼80% of RGCs within 2 weeks. To identify expression programs associated with differential resilience, we first used single-cell RNA-seq (scRNA-seq) to generate a comprehensive molecular atlas of 46 RGC types in adult retina. We then tracked their survival after ONC; characterized transcriptomic, physiological, and morphological changes that preceded degeneration; and identified genes selectively expressed by each type. Finally, using loss- and gain-of-function assays in vivo, we showed that manipulating some of these genes improved neuronal survival and axon regeneration following ONC. This study provides a systematic framework for parsing type-specific responses to injury and demonstrates that differential gene expression can be used to reveal molecular targets for intervention. |
| first_indexed | 2024-09-23T09:55:37Z |
| format | Article |
| id | mit-1721.1/136567 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:55:37Z |
| publishDate | 2021 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1365672023-12-22T20:53:37Z Single-Cell Profiles of Retinal Ganglion Cells Differing in Resilience to Injury Reveal Neuroprotective Genes Tran, Nicholas M Shekhar, Karthik Whitney, Irene E Jacobi, Anne Benhar, Inbal Hong, Guosong Yan, Wenjun Adiconis, Xian Arnold, McKinzie E Lee, Jung Min Levin, Joshua Z Lin, Dingchang Wang, Chen Lieber, Charles M Regev, Aviv He, Zhigang Sanes, Joshua R Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT © 2019 Elsevier Inc. Neuronal types in the central nervous system differ dramatically in their resilience to injury or other insults. Here we studied the selective resilience of mouse retinal ganglion cells (RGCs) following optic nerve crush (ONC), which severs their axons and leads to death of ∼80% of RGCs within 2 weeks. To identify expression programs associated with differential resilience, we first used single-cell RNA-seq (scRNA-seq) to generate a comprehensive molecular atlas of 46 RGC types in adult retina. We then tracked their survival after ONC; characterized transcriptomic, physiological, and morphological changes that preceded degeneration; and identified genes selectively expressed by each type. Finally, using loss- and gain-of-function assays in vivo, we showed that manipulating some of these genes improved neuronal survival and axon regeneration following ONC. This study provides a systematic framework for parsing type-specific responses to injury and demonstrates that differential gene expression can be used to reveal molecular targets for intervention. 2021-10-27T20:36:01Z 2021-10-27T20:36:01Z 2019 2021-02-03T12:52:50Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/136567 en 10.1016/J.NEURON.2019.11.006 Neuron Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | Tran, Nicholas M Shekhar, Karthik Whitney, Irene E Jacobi, Anne Benhar, Inbal Hong, Guosong Yan, Wenjun Adiconis, Xian Arnold, McKinzie E Lee, Jung Min Levin, Joshua Z Lin, Dingchang Wang, Chen Lieber, Charles M Regev, Aviv He, Zhigang Sanes, Joshua R Single-Cell Profiles of Retinal Ganglion Cells Differing in Resilience to Injury Reveal Neuroprotective Genes |
| title | Single-Cell Profiles of Retinal Ganglion Cells Differing in Resilience to Injury Reveal Neuroprotective Genes |
| title_full | Single-Cell Profiles of Retinal Ganglion Cells Differing in Resilience to Injury Reveal Neuroprotective Genes |
| title_fullStr | Single-Cell Profiles of Retinal Ganglion Cells Differing in Resilience to Injury Reveal Neuroprotective Genes |
| title_full_unstemmed | Single-Cell Profiles of Retinal Ganglion Cells Differing in Resilience to Injury Reveal Neuroprotective Genes |
| title_short | Single-Cell Profiles of Retinal Ganglion Cells Differing in Resilience to Injury Reveal Neuroprotective Genes |
| title_sort | single cell profiles of retinal ganglion cells differing in resilience to injury reveal neuroprotective genes |
| url | https://hdl.handle.net/1721.1/136567 |
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