Molecular characterization and functional insights of secondary hair follicles across the cashmere growth cycle

Cashmere production relies on the circannual regeneration of secondary hair follicles (SHFs), yet the precise timing, morphology, and molecular regulation of the SHF cycle in cashmere goats remain incompletely defined. In the present study, we integrate a year-long longitudinal histological analysis with SHF-specific transcriptomic profiling to establish a comprehensive framework of SHF dynamics in Liaoning cashmere goats. High-resolution morphological observation reveals the full-cycle alterations in SHF architecture. Microscopically isolated SHFs yielded expression profiles that accurately defined follicular states and unequivocally distinguished anagen, catagen, and telogen. Across the annual cycle, the telogen-to-early anagen transition emerges as the dominant regulatory shift, accounting for the majority of differentially expressed genes. These signatures function in coordinated opposing patterns, converging on pathways involved in stem cell priming, follicle reactivation, metabolism, and tissue remodeling. In contrast, anagen is characterized by upregulation of genes governing translation, RNA processing, oxidative phosphorylation, and thermogenesis, reflecting the elevated biosynthetic demand during fiber elongation. We further delineate phase-specific regulation of KRT and KRTAP gene families, revealing distinct temporal regulation with direct implications for fiber quality. Co-expression network analysis identifies four major gene modules aligned with specific phases, including a large telogen-enriched module that underscores the transcriptional activity of this traditionally quiescent state. In summary, this study delivers a refined, biologically validated model of the annual SHF cycle, offering new mechanistic insight into the molecular programs that orchestrate seasonal cashmere growth and shedding.