Exploring the function of immune cells in the heart of high-altitude yaks based on transcriptomic sequencing data

Hypoxia can affect the redox state of animal tissue cells, leading to endoplasmic reticulum（ER）stress. The heart plays a crucial role in the regulation of oxygen supply and demand in the body and is particularly susceptible to damage under ER stress. Yaks, which live year-round in high-altitude hypoxic environments, have adapted well to these conditions. However, the changes in immune cell functions within the hearts of high-altitude yaks in response to hypoxia-induced endoplasmic reticulum (ER) stress are not yet fully understood. To address this, we selected yaks from two different altitudes in Qinghai Province, China: Qumalai County (4 500 m) and Xunhua County (2 600 m). We then used transcriptome and single-cell transcriptome sequencing to investigate differences in immune-related gene expression and functional changes in major immune cells in the hearts of yaks from high and low altitudes. This study aims to deepen our understanding of the adaptive changes in the immune characteristics of yak heart tissues. The results from transcriptome sequencing data showed that, compared to low-altitude yaks, upregulated genes in the hearts of high-altitude yaks were primarily enriched in pathways related to ER stress, damaged cell clearance, and the removal of misfolded proteins, all of which are associated with immune function. Gene Set Enrichment Analysis (GSEA) revealed that pathways related to ER stress, damaged cell clearance, and the removal of misfolded proteins were activated in the heart tissues of high-altitude yaks. RT-qPCR experiments confirmed that the expression levels of immune-related genes (eg.LCP1, HLA-A, IGHM, FCGR3) were significantly higher in the heart tissues of high-altitude yaks compared to those of low-altitude yaks (P < 0.05), and the expression trends were consistent with the transcriptome results. Single-cell transcriptome sequencing results showed a decrease in the frequency of lymphocytes, macrophages, and dendritic cells in the heart tissues of high-altitude yaks. Furthermore, the sequencing revealed that upregulated genes in these three types of immune cells in high-altitude yaks were significantly enriched in immune pathways, including Fcγ-R-mediated phagocytosis, T-cell receptor signaling, and antigen processing and presentation, all of which are involved in the clearance of cellular foreign bodies. In summary, the enhanced phagocytic, cytotoxic, and immune complex clearance capabilities of immune cells in the hearts of high-altitude yaks effectively ensure the removal of increased misfolded proteins and other foreign bodies induced by ER stress. This adaptation helps them better cope with the high-altitude hypoxic environment.