Identification of key HIF-1α target genes that regulate adaptation to hypoxic conditions in Tibetan chicken embryos

Abstract

Tibetan chicken, a unique plateau breed, has a suite of adaptive features that enable it to tolerate the high-altitude hypoxic environment. HIF‐1α (hypoxia inducible factor 1 subunit alpha) is a crucial mediator of the cellular response to hypoxia. HIF‐1α maintains oxygen homeostasis by inducing glycolysis, erythropoiesis, and angiogenesis. In this study, using ChIP-seq, we analyzed HIF‐1α binding regions in the chorioallantoic membrane (CAM) tissue of embryos, and identified differential HIF-1α target genes (DTGs) by comparing Chahua (CH) and Tibetan chicken (TC) that had distinct genetic performances, associated with hypoxic adaptation. We identified 752 HIF-1α target genes (TGs), of which 112 were DTGs between the two breeds. We found that eight genes (PTK2, GPNMB, CALD1, CBWD1, SLC25A1, SPRY2, NUPL2, and ST8SIA3) play important roles in hypoxic adaptation by regulating blood vessel development, energy metabolism through angiogenesis, vascular smooth muscle contraction, and various hypoxia-related signaling pathways (including VEGF and PI3K-Akt) in Tibetan chickens during embryonic development. This study enhances our understanding of the molecular mechanisms of hypoxic adaptation in Tibetan chickens and provides new insights into adaptation to hypoxia in humans and other species living at high altitude.