Single-Cell Profiles of Retinal Ganglion Cells Differing in Resilience to Injury Reveal Neuroprotective Genes.
Journal
Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320
Informations de publication
Date de publication:
18 12 2019
18 12 2019
Historique:
received:
24
07
2019
revised:
25
09
2019
accepted:
29
10
2019
pubmed:
1
12
2019
medline:
24
3
2020
entrez:
1
12
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31784286
pii: S0896-6273(19)30969-9
doi: 10.1016/j.neuron.2019.11.006
pmc: PMC6923571
mid: NIHMS1543498
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1039-1055.e12Subventions
Organisme : NEI NIH HHS
ID : R01 EY021526
Pays : United States
Organisme : NEI NIH HHS
ID : R00 EY029360
Pays : United States
Organisme : NEI NIH HHS
ID : F32 EY028448
Pays : United States
Organisme : NEI NIH HHS
ID : R00 EY028625
Pays : United States
Organisme : NEI NIH HHS
ID : K99 EY028625
Pays : United States
Organisme : NIA NIH HHS
ID : R00 AG056636
Pays : United States
Organisme : NIA NIH HHS
ID : K99 AG056636
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH105960
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY012196
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS104248
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS029169
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD090255
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY026939
Pays : United States
Organisme : NEI NIH HHS
ID : K99 EY029360
Pays : United States
Organisme : NINDS NIH HHS
ID : R37 NS029169
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY030204
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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