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.

近来，先天免疫信号通过改变表观遗传环境从而促进转录，在核重编程中起着重要作用。然而，在多能干细胞中将先天性免疫激活和代谢调节联系起来的机制仍然不清楚，尤其是在关键分子成分方面。在这项研究中，我们表明缺氧诱导因子1α（HIF1α）是适应限制氧张力的中央调节剂，是先天性免疫介导的核重编程的意外但至关重要的调节剂。HIF1α是Toll样受体3（TLR3）信号转导的显着上调，对于有效诱导多能性和转分化是必需的。生物能学研究表明，HIF1α通过其在糖酵解开关中已确立的作用来调节先天性免疫介导的重编程。我们相信，这些研究的结果可以帮助我们更好地了解免疫信号在组织再生中的影响，并带来新的治疗策略。