Single-cell atlas reveals cellular heterogeneity and BMP5-mediated regulation of adipogenic differentiation in sheep adipose tissue

Adipose tissue is a heterogeneous multifunctional organ, and understanding depot-specific cellular and molecular diversity reveals functional differences. Here, We construct a single-cell atlas of major adipose depots in sheep, providing foundational data for understanding regional fat deposition. We identify depot-specific adipocytes, with visceral fat (ACSS3+ADC3) and subcutaneous fat (SCD+ADC2) showing distinct adipocyte populations, and tail fat containing a specific type of fibroadipogenic progenitor cells (PDGFRA+ASPC2). Focusing on the unique tail fat of fat-tailed sheep, we conduct longitudinal developmental analyses and identify the BMP signaling pathway as a key upstream regulator of adipogenesis, with bone morphogenetic protein 5 (BMP5) as a critical ligand. We show that knockdown of BMP5 significantly reduces triglyceride accumulation in adipocytes. Collectively, this study indicates that subcutaneous fat is primarily involved in lipid metabolism, whereas visceral fat is linked to metabolic and immune homeostasis. Moreover, BMP5 was identified as a key candidate gene regulating tail fat development. These findings provide potential molecular targets for regulating fat deposition in livestock breeding and offer a valuable resource for studying adipose tissue biology in large mammals.