Insights from Tandem Mass Tag (TMT) Proteomic Analysis on Protein Network Modification in Control of Yak Hair Follicle Cycle

Highland animals have unique hair growth mechanisms to allow them to adapt to harsh living environments. Compared with other species, their hair cycle growth is affected by more environmental factors. Yaks, as highland animals, have obvious periodic hair growth characteristics in a year; this biological process is regulated by numerous proteins, but the specific molecular regulatory mechanism is still unclear. Here we analyzed the histological characteristics of yak hair follicles (HFs) at each stage and conducted TMT proteomics research. The protein expression network of yak hair at each stage and the mechanism of the yak HF growth cycle were systematically explored, and the candidate proteins Sfrp1 and Ppard were verified. A total of 3176 proteins were quantifiable and 1142 differentially expressed proteins (DEPs) were obtained at five stages of the yak hair cycle. DEPs enriched in complement activation change, tissue development, lipid metabolism, WNT pathway, VEGF pathway, JAK-STAT pathway, and PPAR pathway may promote the growth of yak hair follicles, such as Serpinf1, Ppard, and Stat3. DEPs enriched in complement system, coagulation, cell adhesion, lipid metabolic process, proliferation of epidermal cells, and estrogen pathway may promote the degeneration of yak hair, such as Sfrp1, Eppk1, and Egfr. Using Protein-Protein Interaction (PPI) analysis, we found that core nodes of DEP networks in yak skin are significantly different at three critical time points in hair follicle development, and lipid metabolism proteins are common core DEP nodes during yak HF growth and degeneration. The expression of Sfrp1 and Ppard in yak hair follicles at different periods showed they are related to yak hair cycle control. This study showed that the protein regulatory network of the yak HF growth cycle is complex and dynamically changing and revealed key candidate proteins that may affect yak hair follicle development. These findings provided detailed data for further understanding of the plateau adaptation mechanism of the yak, which is of great significance to make better use of the yak livestock resources and enhance their economic value.