Stem Cell Reports
Volume 14, Issue 2, 11 February 2020, Pages 192-200
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HIF1α Regulates Early Metabolic Changes due to Activation of Innate Immunity in Nuclear Reprogramming

https://doi.org/10.1016/j.stemcr.2020.01.006Get rights and content
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Highlights

  • HIF1α is dramatically upregulated as a consequence of TLR3 signaling

  • HIF1α is necessary for efficient induction of pluripotency and transdifferentiation

  • HIF1α regulates innate immune-mediated reprogramming by inducing a glycolytic switch

Summary

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.

Keywords

innate immunity
nuclear reprogramming
transdifferentiation
hypoxia-inducible factor 1
glycolysis
iPSCs
endothelial cells
regeneration
metabolism
chromatin

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Co-first author