Transcription factor-based direct conversion of human fibroblasts to functional astrocytes.
Nfia
Nfib
Sox9
astrocytes
direct conversion
fibroblasts
neurodegenerative diseases
neurons
transcription factors
transdifferentiation
Journal
Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300
Informations de publication
Date de publication:
12 07 2022
12 07 2022
Historique:
received:
24
09
2021
revised:
20
05
2022
accepted:
23
05
2022
pubmed:
25
6
2022
medline:
16
7
2022
entrez:
24
6
2022
Statut:
ppublish
Résumé
Astrocytes are emerging key players in neurological disorders. However, their role in disease etiology is poorly understood owing to inaccessibility of primary human astrocytes. Pluripotent stem cell-derived cells fail to mimic age and due to their clonal origin do not mimic genetic heterogeneity of patients. In contrast, direct conversion constitutes an attractive approach to generate human astrocytes that capture age and genetic diversity. We describe efficient direct conversion of human fibroblasts to functional induced astrocytes (iAs). Expression of the minimal combination Sox9 and Nfib generates iAs with molecular, phenotypic, and functional properties resembling primary human astrocytes. iAs could be obtained by conversion of fibroblasts covering the entire human lifespan. Importantly, iAs supported function of induced neurons obtained through direct conversion from the same fibroblast population. Fibroblast-derived iAs will become a useful tool to elucidate the biology of astrocytes and complement current in vitro models for studies of late-onset neurological disorders.
Identifiants
pubmed: 35750047
pii: S2213-6711(22)00268-5
doi: 10.1016/j.stemcr.2022.05.015
pmc: PMC9287681
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1620-1635Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
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