Genomic structural variation represents a source for genetic and phenotypic variation, which may be subject to selection during the environmental adaptation and population differentiation. Here, we described a genome-wide analysis of copy number variations (CNVs) in 16 populations of yak based on genome resequencing data and CNV-based cluster analyses of these populations. In total, we identified 51,461 CNV events and defined 3174 copy number variation regions (CNVRs) that covered 163.8 Mb (6.2%) of yak genome with more “loss” events than both “gain” and “both” events, and we confirmed 31 CNVRs in 36 selected yaks using quantitative PCR. Of the total 163.8 Mb CNVR coverage, a 10.8 Mb region of high-confidence CNVRs directly overlapped with the 52.9 Mb of segmental duplications, and we confirmed their uneven distributions across chromosomes. Furthermore, functional annotation indicated that the CNVR-harbored genes have a considerable variety of molecular functions, including immune response, glucose metabolism, and sensory perception. Notably, some of the identified CNVR-harbored genes associated with adaptation to hypoxia (e.g., DCC, MRPS28, GSTCD, MOGAT2, DEXI, CIITA, and SMYD1). Additionally, cluster analysis, based on either individuals or populations, showed that the CNV clustering was divided into two origins, indicating that some yak CNVs are likely to arisen independently in different populations and contribute to population difference. Collectively, the results of the present study advanced our understanding of CNV as an important type of genomic structural variation in yak, and provide a useful genomic resource to facilitate further research on yak evolution and breeding.

Skeletal muscle is a complex heterogeneous tissue and characterizing its cellular heterogeneity and transcriptional and epigenetic signatures are important for understanding the details of its ontogeny. In our study, we applied scRNA‐seq and scATAC‐seq to investigate the cell types, molecular features, transcriptional and epigenetic regulation, and patterns of developing bovine skeletal muscle from gestational, lactational and adult stages. Detailed molecular analyses were used to dissect cellular heterogeneity, and we deduced the differentiation trajectory of myogenic cells and uncovered their dynamic gene expression profiles. SCENIC analysis was performed to demonstrate key regulons during cell fate decisions. We explored the future expression states of these heterogeneous cells by RNA velocity analysis and found extensive networks of intercellular communication using the toolkit CellChat. Moreover, the transcriptomic and chromatin accessibility modalities were confirmed to be highly concordant, and integrative analysis of chromatin accessibility and gene expression revealed key transcriptional regulators acting during myogenesis. In bovine skeletal muscle, by scRNA‐seq and scATAC‐seq analysis, different cell types such as adipocytes, endothelial cells, fibroblasts, lymphocytes, monocytes, pericyte cells and eight skeletal myogenic subpopulations were identified at the three developmental stages. The pseudotime trajectory exhibited a distinct sequential ordering for these myogenic subpopulations and eight distinct gene clusters were observed according to their expression pattern. Moreover, specifically expressed TFs (such as MSC, MYF5, MYOD1, FOXP3, ESRRA, BACH1, SIX2 and ATF4) associated with muscle development were predicted, and likely future transcriptional states of individual cells and the developmental dynamics of differentiation among neighbouring cells were predicted. CellChat analysis on the scRNA‐seq data set then classified many ligand–receptor pairs among these cell clusters, which were further categorized into significant signalling pathways, including BMP, IGF, WNT, MSTN, ANGPTL, TGFB, TNF, VEGF and FGF. Finally, scRNA‐seq and scATAC‐seq results were successfully integrated to reveal a series of specifically expressed TFs that are likely to be candidates for the promotion of cell fate transition during bovine skeletal muscle development. Overall, our results outline a single‐cell dynamic chromatin/transcriptional landscape for normal bovine skeletal muscle development; these provide an important resource for understanding the structure and function of mammalian skeletal muscle, which will promote research into its biology.

Due to its prominent secretory activity, adipose tissue (AT) is now considered a major player in the crosstalk between organs, especially with skeletal muscle. In which, exosomes are effective carriers for the intercellular material transfer of a wide range of molecules that can influence a series of physiological and pathological processes in recipient cells. Considering their underlying roles, the regulatory mechanisms of adipose-secreted exosomes and their cellular crosstalk with skeletal muscle have received great attention in the field. In this review, we describe what is currently known of adipose-secreted exosomes, as well as their applications in skeletal muscle pathophysiology.

Yaks have evolved several breeds or genetic resources owing to their geographical and ecological environment, and investigating the genetic construction of body size among breeds is key for breeding. Here, a genome-wide association study (GWAS) was performed for five body size traits in 31 yak breeds and genetic resources. The information from clustering individuals according to their habitats was used for kinship grouping in the compressed mixed linear model (CMLM). We named this approach the pCMLM method. A total of 3,584,464 high-quality single nucleotide polymorphisms (SNPs) were obtained, and six markers were found to be significantly associated with height by pCMLM. Four candidate genes, including FXYD6, SOHLH2, ADGRB2, and OSBPL6, were identified. Our results show that when CMLM cannot identify optimal clustering groups, pCMLM can provide sufficient associated results based on population information. Moreover, this study provides basic information on the gene localization of quantitative traits of body size among yak breeds.

The yak (Bos grunniens) has exceptional hypoxia resilience, making it an ideal model for studying high-altitude adaptation. Here, we investigated the effects of oxygen concentration on yak cardiac fibroblast proliferation and the underlying molecular regulatory pathways using RNA sequencing (RNA-seq) and metabolic analyses. Decreased oxygen levels significantly inhibited cardiac fibroblast proliferation and activity. Intriguingly, while the mitochondrial DNA (mtDNA) content remained stable, we observed coordinated upregulation of mtDNA-encoded oxidative phosphorylation components. Live-cell metabolic assessment further demonstrated that hypoxia led to mitochondrial respiratory inhibition and enhanced glycolysis. RNA-seq analysis identified key hypoxia adaptation genes, including glycolysis regulators (e.g., HK2, TPI1), and hypoxia-inducible factor 1-alpha (HIF-1α), with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses highlighting their involvement in metabolic regulation. The protein–protein interaction network identified three consensus hub genes across five topological algorithms (CCNA2, PLK1, and TP53) that may be involved in hypoxia adaptation. These findings highlight the importance of metabolic reprogramming underlying yak adaptation to hypoxia, providing valuable molecular insights into the mechanisms underlying high-altitude survival.