Book Description

The Human Cell Atlas is an international initiative aiming at creating a comprehensive map of all cells in the human body. This project contributes to the Skin Atlas by attempting to resolve a population of interfollicular epidermal stem cells (IFE SCs), previously described as homogeneous. These cells are located in the basal layer of the epidermis, which is distinguished by high expression of a6-integrin. We used this marker to enrich keratinocytes from human skin for basal cells and perform single-cell RNA sequencing.We found three transcriptionally distinct populations of basal keratinocytes. Two of them expressed classic basal layer markers KRT5, KRT14. The differences between these stem cells were driven by genes associated with immunomodulatory function (CCL2, CXCL14, POSTN). The third population of basal keratinocytes was enriched in markers of early stem cell commitment (KRT10, DMKN). The three groups formed a continuous trajectory after pseudotime reconstruction, reflecting differentiation of IFE SCs.We used the same approach to address changes that IFE SCs undergo in psoriasis, an auto-immune disease characterized by skin inflammation and keratinocyte hyperproliferation. We found that basal cells from psoriatic epidermis also have two stem cell sub-populations and one group with the early differentiated signature. The latter was expanded from 8% in healthy skin to 33% in psoriasis. We were also able to identify sub-populations of stem cells that are specific to healthy and disease skin and found non-linear pseudotime trajectory of basal cells in psoriasis, suggesting a stem cell state switch in disease. In conclusion, the Skin Atlas is founding new insights in the epidermal stem cell compartment in healthy and diseased skin.