Deciphering the cellular landscape and genetic underpinnings of fiber diameter determined by dermal papilla cells in fine-wool sheep.

Wool fiber diameter (FD) is a key economic trait in fine-wool sheep, and its growth process is closely associated with the development and cyclical growth of hair follicles (HFs). Therefore, a comprehensive understanding of the molecular mechanisms regulating HF development is of significant importance. In this study, single-cell RNA sequencing (scRNA-seq) was performed on skin tissues from six half-sibling fine-wool sheep reared under identical conditions but exhibiting different fiber diameters, successfully constructing a transcriptional atlas of the HF microenvironment. A total of 59,732 high-quality cells were captured and systematically annotated into 14 distinct cell types using known marker genes. Each cell type exhibited unique gene expression profiles. Analysis of cell proportions across the three experimental groups revealed that the ultra-fine group had a higher proportion of dermal papilla cells (DPCs), hair follicle stem cells (HFSC), and outer root sheath cells (ORS) compared to the other two groups. Cell-cell communication analysis identified multiple ligand-receptor pairs involved in HF regulation, suggesting that DPCs may play an important role in modulating HF growth and development. Pseudotime trajectory analysis reconstructed the developmental dynamics of the epidermal lineage. Furthermore, we identified that DPCs may exist in three distinct states to perform their physiological functions. To elucidate the molecular mechanisms underlying FD, we identified and analyzed differentially expressed genes across cell types in the ultra-fine, medium-fine, and fine wool groups, and performed cellular-level validation of