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

TL;DR

This study uses a single-cell atlas to explore fat tissue diversity in sheep and identifies BMP5 as a key gene regulating fat development.

Contribution

The study provides a single-cell atlas of sheep adipose depots and identifies BMP5 as a critical regulator of tail fat development.

Findings

Visceral and subcutaneous fat in sheep have distinct adipocyte populations marked by ACSS3/ADC3 and SCD/ADC2, respectively.

Tail fat contains PDGFRA+ASPC2 fibroadipogenic progenitor cells, and BMP5 is a key regulator of adipogenesis in this tissue.

Knockdown of BMP5 reduces triglyceride accumulation in adipocytes, suggesting its role in fat deposition.

Abstract

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.

Single-cell atlas reveals depot-specific cellular diversity of sheep adipose tissues, identifying BMP5 as a key candidate ligand gene regulating tail fat development.

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