Single-Cell Transcriptomics Reveals the Differentiation and Spatial Signatures underlying Sheep Hair Follicle Heterogeneity and Wool Curvature

Here, Single-cell suspensions from the wavy wool and straight wool lambskins were prepared for unbiased single-cell RNA sequencing (scRNA-seq). Based on UAMP analysis, we identified 19 distinct populations from 15,830 single-cell transcriptomes and delineated their cellular identity from specific gene expression profiles. Furtherly, novel marker gene was applied in identifying dermal papilla cells isolated in vitro. By using pseudotime ordering analysis, we successfully constructed the epithelium cell lineage differentiation trajectory and revealed the dynamic gene expression profiles of matrix progenitors' commitment to the hair shaft and inner root sheath (IRS) cells. Meanwhile, intercellular communication between different cell populations was inferred based on CellChat and the priori knowledge of ligand-receptor pairs, as a result strong intercellular communication and associated signaling pathways were revealed. Besides, to clarify the molecular mechanism of wool curvature, differentially expressed genes in specific cells between straight wool and curly wool were identified and analyzed. Our findings here provide unbiased and systematic view of transcriptional organization of sheep hair follicle, reveal the differentiation and spatial signatures underlying sheep hair follicle heterogeneity and wool curvature, which will provide a valuable resource for understanding the molecular pathways involved in sheep hair follicle development. Overall design: To gain insight into the transcriptional heterogeneity of the anagen hair follicle cells and the molecular mechanisms of wool curvature, we performed scRNA-seq on Hu sheep skins from straight wool individuals and waved wool individuals. We detected 19,097 genes in skin cells for straight wool group and 19,059 genes for waving wool group. After removing low quality cells, we obtained 15830 single-cell transcriptome profiles from these two groups (7,263 for straight wool group and 8,567 single cells for waving wool group)