A Single-Cell Atlas of Sheep White Adipose Tissue and Cellular Heterogeneity in Tail Fat Development

Adipose tissue is not only a storage site for energy but also a highly heterogeneous and plastic endocrine and immune organ. Exploring the cellular and molecular heterogeneity of different fat depots is crucial for understanding their functions; however, research on sheep fat depots remains at the bulk level. Here, for the first time, single-nucleus RNA sequencing was used to characterize four representative fat depots in Hu sheep, including dorsal subcutaneous fat, perirenal fat, mesenteric fat, and the sheep-specific tail fat. We constructed a single-cell atlas of four fat depots, including nine cell subtypes such as adipose cells (6 subclusters), adipose stem and progenitor cells (5 subclusters), endothelial cells, and macrophage cells. We observed depot-specific adipocytes, with visceral fat (ADC3) and subcutaneous fat (ADC2) showing distinct adipocyte populations, and tail fat containing a specific type of fibroadipogenic progenitor cells (ASPC2). To analyze the cellular heterogeneity of tail fat development, we selected 4 key developmental stages in sheep to characterize tail fat cells, identifying the ASPC4 subcluster that plays a role in differentiation during early development. Additionally, we identified the BMP pathway (BMP5 - BMPR1A / ACVR2A) as playing an important role in cell communication during early adipocyte differentiation, which may help enhance regulation of tail fat deposition. Altogether, our work provides a robust data foundation and new insights for studying the localized deposition of fat in sheep and the unique functions of different fat depots, serving as a fundamental resource for future regulation of fat deposition in sheep.