IRF2 is a master regulator of human keratinocyte stem cell fate.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
14 10 2019
14 10 2019
Historique:
received:
09
11
2018
accepted:
14
09
2019
entrez:
16
10
2019
pubmed:
16
10
2019
medline:
14
1
2020
Statut:
epublish
Résumé
Resident adult epithelial stem cells maintain tissue homeostasis by balancing self-renewal and differentiation. The stem cell potential of human epidermal keratinocytes is retained in vitro but lost over time suggesting extrinsic and intrinsic regulation. Transcription factor-controlled regulatory circuitries govern cell identity, are sufficient to induce pluripotency and transdifferentiate cells. We investigate whether transcriptional circuitry also governs phenotypic changes within a given cell type by comparing human primary keratinocytes with intrinsically high versus low stem cell potential. Using integrated chromatin and transcriptional profiling, we implicate IRF2 as antagonistic to stemness and show that it binds and regulates active cis-regulatory elements at interferon response and antigen presentation genes. CRISPR-KD of IRF2 in keratinocytes with low stem cell potential increases self-renewal, migration and epidermis formation. These data demonstrate that transcription factor regulatory circuitries, in addition to maintaining cell identity, control plasticity within cell types and offer potential for therapeutic modulation of cell function.
Identifiants
pubmed: 31611556
doi: 10.1038/s41467-019-12559-x
pii: 10.1038/s41467-019-12559-x
pmc: PMC6791852
doi:
Substances chimiques
IRF2 protein, human
0
Interferon Regulatory Factor-2
0
Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4676Références
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