Abstract: As the most important organ for blood circulation, the heart plays an important role in the environmental adaptation of animals. Cardiomyocyte is the main functional cell in the animal heart, however, gene expression changes and cellular communication in cardiomyocytes of yaks living at high altitudes are still unclear. To study the effect of yak cardiomyocytes in the process of adaptation to the plateau environment, yaks in high altitude areas (Qilian, Qinghai, altitude 4000 m) and low altitude areas (Xunhua, Qinghai, altitude 2 600 m) were taken as research objects, and the cellular communications and ligand-target gene regulations in cardiomyocytes and other cells were predicted based on the 10× singlecell RNA sequencing data. In addition, the functions of differentially expressed genes (DEGs) between different altitude yak cardiomyocytes were annotated. The results showed that yak cardiomyocytes were most highly correlated with the endothelial cells and epithelial cells. The expression level of ligand and receptor of CD74_COAP and CD74_APP was relatively higher in the cardiomyocyte-dendritic cell and cardiomyocyte-macrophage, the vitality of ligands and receptors was relatively higher in TNF signal pathway; The immune related pathway ligands, such as PTPRC, PECAM1, ITGB2, ANXA1, BDNF had a significant influence on all ‘cell pairs’and the PI3K-Akt signal pathway showed the highest potential score in ligand-target gene regulation; The functions of DEGs between high and low altitude yak cardiomyocytes were mainly enriched in metabolic pathways as the oxidative phosphorylation and glycolysis pathways. These results suggest that yaks may maintain their homeostasis by strengthening the connection between cardiomyocytes and other cells and regulating the processes related to immune action. Meanwhile, high-altitude yaks enhance their aerobic and anaerobic metabolism of cardiomyocytes to acquire more energy to adapt to the harsh environment of high altitude.

Key words: Yak, Cardiomyocytes, scRNA-seq, Plateau environment adaptation

摘要： 心脏作为血液循环最重要的器官在动物环境适应中发挥着重要的作用。心肌细胞是心脏主要的功能细胞，然而高海拔地区牦牛心肌细胞基因表达变化及细胞间通讯关系尚不清楚。为此，本研究以高海拔地区牦牛 (青海祁连，海拔 4 000 m) 和低海拔地区牦牛 (青海循化，海拔 2 600 m) 为研究对象，基于心脏组织 10 × 单细胞转录组测序数据，对心肌细胞和心脏其他细胞进行细胞通讯及配体-靶基因调控预测，同时对高、低海拔牦牛心肌细胞差异表达基因进行功能注释分析，以期探究心肌细胞在牦牛适应高原环境过程中的作用。结果显示，牦牛心肌细胞与内皮细胞、上皮细胞的关联最强，心肌细胞-树突状细胞及心肌细胞-巨噬细胞两个“细胞对”中CD74_COAP 和 CD74_APP 配受体表达量相对较高；配受体活力在 TNF 信号通路中相对较强；在免疫相关通路发挥重要作用的配体 PTPRC、PECAM1、ITGB2、ANXA1、BDNF 等对所有“细胞对”影响明显，且 PI3K-Akt 信号通路在配体-靶基因调控中潜力分值最高；高、低海拔牦牛心肌细胞中差异表达基因功能主要富集在代谢途径，其中氧化磷酸化、糖酵解代谢通路相关的基因表达明显增强。本研究结果提示，牦牛可通过加强心肌细胞与其他细胞之间的联系及调节免疫作用相关过程维持自身稳态；同时高海拔牦牛可通过增强心肌细胞有氧代谢和无氧代谢进而获取更多能量以适应高海拔严酷环境。

关键词: 牦牛, 心肌细胞, 单细胞转录组测序, 高原环境适应