Development and regulation of stem cell lineages in skin

National Institute Of Arthritis And Musculoskeletal And Skin Diseases

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Abstract

Following up on prior work that identified the perineural microenvironment as a regulator of hair follicle stem cells, we have completed a project describing a perivascular niche for hair follicle stem cells. Moreover, we have identified that sensory touch domes in the skin, and the Merkel cells housed there are also regulated by associated Shh signaling from sensory neurons. We have continued experiments demonstrating that touch domes are a novel and distinct cell lineage within the skin maintained by their own stem cell population. We have also investigated the developmental requirements for Merkel cell formation in skin. We have found that establishing the Merkel cell touch dome lineage in embryonic skin requires a cascade of Wnt, Eda, and intraepithelial Shh signaling. We have identified multiple transcriptional networks that are responsible for formation or maintenance of Merkel cells in mouse skin. Ongoing work using single cell RNA-seq and ATAC-seq investigates the transcriptional requirements for Merkel cell differentiation. We are applying our understanding of Merkel cell development to generate an in vitro differentiation model of Merkel cell formation. These studies have identified neuroendocrine lineage factors that are important for both normal Merkel cell formation and are critical in Merkel cell carcinoma.