PDGFD Maintains Ovine Tail ADSCs in a Proliferative State by Suppressing CXCL8 and Activating PI3K/MAPK Signaling

Min Yang^1*Jilong Han¹Qianqian Liang¹Jie Zhang¹Xianshu Wang¹Beibit Turganbekovich Kulatayev²Mahaba Rouzi³Pengcheng Wan^4*

• ¹Shihezi University, Shihezi, China
• ²Kazakh National Agrarian Research University, Almaty, Kazakhstan
• ³Xinjiang Uygur Autonomous Regional Animal Husbandry Station, Urumqi, China
• ⁴Xinjiang Academy of Agricultural and Reclamation Science, Shihezi, China

The fat tail in sheep is a distinctive adaptive trait, yet the cellular mechanisms controlling its development are poorly understood. Although PDGFD is a high-priority candidate gene from selective sweep analyses, its precise cellular function and underlying molecular mechanisms remain uncharacterized. In this study, we 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). PDGFD knockdown significantly inhibited ADSCs proliferation and concurrently upregulated key adipogenic markers (PPARγ, FABP4), suggesting its critical role in maintaining a proliferative, undifferentiated progenitor state. Transcriptomic profiling revealed that this phenotype was mediated primarily through the profound downregulation of the chemokine CXCL8. Subsequent pathway analysis demonstrated that the PDGFD-CXCL8 axis co-regulates adipose plasticity by modulating the activity of both the PI3K-Akt and MAPK signaling pathways. 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.