Single-cell transcriptomic survey of cell diversity and functional changes in yak hearts at different altitude.

The yak (Bos grunniens) is a species adapted to the hypoxic environment in the plateau area. The heart is a hypoxia-sensitive organ involved in this adaptation. Herein, we used single-cell RNA-seq technology and clustering to determine the presence of 11 cell populations in the yak heart. We analyzed gene expression differences and expression patterns in each cell subpopulation at different altitudes. The cells related to altitude changes are mainly smooth muscle cells and vascular endothelial cells. Of the four transcription factors (TFs, MEF2B, FOXP4, ARID5A, and HES4) found in smooth muscle cells, only MEF2B was specifically expressed in vascular smooth muscle cells. Three key TFs (HNF1B, DMRTA1, and ARNTL2) were also found in the cardiomyocyte module. Compared with data extracted from low-altitude yak, we observed that the high altitude yak has enhanced contraction and relaxation of vascular smooth muscle cells and an increased metabolic level of cardiomyocytes. These may be strategies for the yak to adapt to high-altitude hypoxia environments.