HIF1α Regulates Early Metabolic Changes due to Activation of Innate Immunity in Nuclear Reprogramming.
Animals
Cell Nucleus
/ drug effects
Cell Transdifferentiation
/ drug effects
Cellular Reprogramming
/ drug effects
Fibroblasts
/ drug effects
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
/ metabolism
Immunity, Innate
/ drug effects
Male
Mice, Knockout
Poly I-C
/ pharmacology
Signal Transduction
/ drug effects
Toll-Like Receptor 3
/ agonists
Transcription, Genetic
/ drug effects
chromatin
endothelial cells
glycolysis
hypoxia-inducible factor 1
iPSCs
innate immunity
metabolism
nuclear reprogramming
regeneration
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:
11 02 2020
11 02 2020
Historique:
received:
12
03
2019
revised:
09
01
2020
accepted:
12
01
2020
entrez:
13
2
2020
pubmed:
13
2
2020
medline:
5
2
2021
Statut:
ppublish
Résumé
Innate immune signaling has recently been shown to play an important role in nuclear reprogramming, by altering the epigenetic landscape and thereby facilitating transcription. However, the mechanisms that link innate immune activation and metabolic regulation in pluripotent stem cells remain poorly defined, particularly with regard to key molecular components. In this study, we show that hypoxia-inducible factor 1α (HIF1α), a central regulator of adaptation to limiting oxygen tension, is an unexpected but crucial regulator of innate immune-mediated nuclear reprogramming. HIF1α is dramatically upregulated as a consequence of Toll-like receptor 3 (TLR3) signaling and is necessary for efficient induction of pluripotency and transdifferentiation. Bioenergetics studies reveal that HIF1α regulates the reconfiguration of innate immune-mediated reprogramming through its well-established role in throwing a glycolytic switch. We believe that results from these studies can help us better understand the influence of immune signaling in tissue regeneration and lead to new therapeutic strategies.
Identifiants
pubmed: 32048999
pii: S2213-6711(20)30027-8
doi: 10.1016/j.stemcr.2020.01.006
pmc: PMC7013248
pii:
doi:
Substances chimiques
Hypoxia-Inducible Factor 1, alpha Subunit
0
Toll-Like Receptor 3
0
Poly I-C
O84C90HH2L
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
192-200Subventions
Organisme : NIAID NIH HHS
ID : R01 AI020211
Pays : United States
Organisme : NHLBI NIH HHS
ID : K01 HL135455
Pays : United States
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
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