A miR-124-mediated post-transcriptional mechanism controlling the cell fate switch of astrocytes to induced neurons.
ISX9
Zfp36l1, in vivo reprogramming
astrocytes
direct reprogramming
miR-124
Journal
Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300
Informations de publication
Date de publication:
11 04 2023
11 04 2023
Historique:
received:
14
06
2022
revised:
21
02
2023
accepted:
23
02
2023
medline:
14
4
2023
pubmed:
25
3
2023
entrez:
24
3
2023
Statut:
ppublish
Résumé
The microRNA (miRNA) miR-124 has been employed supplementary to neurogenic transcription factors (TFs) and other miRNAs to enhance direct neurogenic conversion. The aim of this study was to investigate whether miR-124 is sufficient to drive direct reprogramming of astrocytes to induced neurons (iNs) on its own and elucidate its independent mechanism of reprogramming action. Our data show that miR-124 is a potent driver of the reprogramming switch of astrocytes toward an immature neuronal fate by directly targeting the RNA-binding protein Zfp36L1 implicated in ARE-mediated mRNA decay and subsequently derepressing Zfp36L1 neurogenic interactome. To this end, miR-124 contribution in iNs' production largely recapitulates endogenous neurogenesis pathways, being further enhanced upon addition of the neurogenic compound ISX9, which greatly improves iNs' differentiation and functional maturation. Importantly, miR-124 is potent in guiding direct conversion of reactive astrocytes to immature iNs in vivo following cortical trauma, while ISX9 supplementation confers a survival advantage to newly produced iNs.
Identifiants
pubmed: 36963393
pii: S2213-6711(23)00056-5
doi: 10.1016/j.stemcr.2023.02.009
pmc: PMC10147664
pii:
doi:
Substances chimiques
MicroRNAs
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
915-935Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interests The authors declare no competing interests.
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