HIF1α Regulates Early Metabolic Changes due to Activation of Innate Immunity in Nuclear Reprogramming

Chun Liu, Hongyue Ruan, Farhan Himmati, Ming Tao Zhao, Christopher C. Chen, Merna Makar, Ian Y. Chen, Karim Sallam, Edward S. Mocarski, Danish Sayed, Nazish Sayed

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)192-200
Number of pages9
JournalStem Cell Reports
Volume14
Issue number2
DOIs
StatePublished - Feb 11 2020

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

Keywords

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

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