BMPER induces the adipogenic differentiation of fibro/adipogenic progenitors and promotes intramuscular fat deposition in chickens
摘要
Fibro-adipogenic progenitors (FAPs) serve as the developmental origin of intramuscular adipocytes in skeletal muscle. Enhancing their adipogenic transition could increase intramuscular fat (IMF) deposition, thereby improving meat flavor in chickens. However, critical aspects of FAPs including their cellular composition, dynamic changes during skeletal muscle growth, and associated regulatory mechanisms remain poorly understood. Therefore, we comprehensively characterized FAPs in Langshan chickens from d 1 to d 98 using both in vivo and in vitro approaches combined with single-nucleus RNA sequencing (snRNA-seq) analysis.
ResultsOur analysis of IMF contents and adipogenesis-related gene expression in the pectoralis major muscle of Langshan chickens revealed that the adipogenic properties of FAPs peaked at d 1, reached its lowest point at d 14, and subsequently increased until d 98. The snRNA-seq analysis successfully identified the population of FAPs along with their 5 subtypes including the pre-adipogenic, adipogenic, and fibrotic FAPs. The ratio of the pre-adipogenic subtype decreased from d 14 to d 98, which was reversely correlated with the changes of the adipogenic subtype, suggesting a differentiating process. Furthermore, RNA velocity and pseudo-trajectory analysis revealed that the initial FAPs had superior fibrotic capacity but decreased over time which contrasted with their enhanced adipogenic capacity with development. Notably, BMPER was identified as an important regulator for the adipogenic differentiation of FAPs, which was also confirmed by in vitro over-expression studies. In addition, the expression of BMPER in the adipogenic portion of FAPs was found to be highly conserved across human and mouse skeletal muscles.
ConclusionsOur study provides the first comprehensive atlas of FAPs in the skeletal muscle of chickens and identifies BMPER as a key regulator for the adipogenic differentiation of FAPs. The findings will not only provide novel targets for breeding chickens with high IMF content but also offer significant insights into understanding the cell fate decision of FAPs under both physiological and pathological conditions across species.