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The molecular anatomy of mouse skin during hair growth and rest

Skin homeostasis is orchestrated by dozens of cell types that together direct stem cell renewal, lineage commitment and differentiation. However, a systematic molecular atlas of full-thickness skin is lacking. Here, we used single-cell RNA-sequencing and mRNA-FISH to determine gene-expression identity and spatial location of skin cells during hair growth and rest. We defined 55 cell populations and made striking discoveries about the outer root sheath (ORS) and inner hair follicle layers that together coordinate hair production. The ORS is composed of two distinct cell types, companion layer cells resemble ORS and not inner layer cells, and we identified an asymmetric inner-layer structure with ORS cell identity. Moreover, the inner layers branch from transcriptionally uncommitted progenitors, and each lineage differentiation passes through an intermediate state. Altogether, we generated a comprehensive atlas with molecular and spatial information on epithelial and stromal cells, including fibroblasts, vascular and immune cells, that will spur new discoveries in skin biology. HIGHLIGHTS - Comprehensive single-cell transcriptome atlas of full-thickness skin - Outer root sheath (ORS) is composed of two distinct cell types - Companion layer transcriptionally resembles ORS - Transcriptional reconstruction of the internal hair follicle (HF) lineages - Molecular identification of an asymmetric HF-bulb structure - Spatial map of fibroblast subtypes in the skin - Online tool. http://kasperlab.org/tools