Abstract
Introduction The fat tail in sheep is a distinctive adaptive trait, yet the cellular mechanisms controlling its development remain poorly understood. Although PDGFD is a high-priority candidate gene from selective sweep analyses, its precise cellular function and underlying molecular mechanisms are uncharacterized. Methods We first defined E70–E80 as the critical fetal period for the initial formation of rump or tail adipose tissue in sheep. To delineate the functional role of PDGFD , we performed knockdown experiments in ovine adipose-derived stem cells (ADSCs) and conducted transcriptomic profiling. Results PDGFD knockdown significantly inhibited ADSCs proliferation and concurrently upregulated key adipogenic markers ( PPARγ , FABP4 ). Transcriptomics revealed that this phenotype was mediated primarily through the profound downregulation of the chemokine CXCL8 . Pathway analysis demonstrated that the PDGFD-CXCL8 axis co-regulates adipose plasticity by modulating both the PI3K-Akt and MAPK signaling pathways. Conclusion We conclude that PDGFD is a master regulator of adipose tissue plasticity, driving progenitor expansion via a CXCL8-dependent mechanism. This PDGFD-CXCL8 regulatory axis orchestrates the cellular groundwork essential for the extensive fat deposition that defines the ovine fat-tail phenotype.