PSV-A-10 - Single-cell Atlas of Bovine Skeletal Muscle Identifies Mechanisms Regulating Intramuscular Adipogenesis and Fibrogenesis

Abstract: Human and mouse studies have shown that fibro/adipogenic progenitors (FAPs) are a major source of intramuscular fat (IMF) and extracellular matrix (ECM) proteins. IMF and ECM proteins directly influence the palatability of beef, suggesting an essential role of FAPs in beef quality determination, which is still largely unexplored. We performed single-cell RNAseq (scRNAseq) using cells isolated from full blood Wagyu and Brahman cattle and Wagyu/Brahman cross cattle, which identified 21 cell clusters representing FAPs, several endothelial cell types, vascular smooths muscle cells, satellite cells, muscle fibers, and multiple immune cell types. More abundant FAPs were identified in the muscle of Brahman cattle, while a larger number of endothelial cells were identified in the muscle of Wagyu cattle. Further analysis of FAPs identified multiple FAP subpopulations with distinct gene expression profiles and anatomic locations. GSEA analysis revealed adipogenic and fibrogenic FAP subpopulations. A comparison of FAP subpopulations among different breeds showed higher complement system activity in the adipogenic FAP subpopulation of Wagyu cattle. Forced activation of the complement system in FAPs enhanced their adipogenic efficiency in vitro. In addition, cell-cell communication analysis identified active interactions between FAPs and other cell types through direct contact and secreted factors, many of which may affect FAP activities. In conclusion, our study revealed the single-cell atlas of bovine skeletal muscle and identified mechanisms regulating bovine intramuscular adipogenesis and fibrogenesis.