Identification of Stem Cell Populations in Sweat Glands and Ducts Reveals Roles in Homeostasis and Wound Repair

Sweat glands are abundant in the body and essential for thermoregulation. Like mammary glands, they originate from epidermal progenitors. However, they display few signs of cellular turnover, and whether they have stem cells and tissue-regenerative capacity remains largely unexplored. Using lineage tracing, we here identify in sweat ducts multipotent progenitors that transition to unipotency after developing the sweat gland. In characterizing four adult stem cell populations of glandular skin, we show that they display distinct regenerative capabilities and remain unipotent when healing epidermal, myoepithelial-specific, and lumenal-specific injuries. We devise purification schemes and isolate and transcriptionally profile progenitors. Exploiting molecular differences between sweat and mammary glands, we show that only some progenitors regain multipotency to produce de novo ductal and glandular structures, but that these can retain their identity even within certain foreign microenvironments. Our findings provide insight into glandular stem cells and a framework for the further study of sweat gland biology. [Display omitted] ► Populations of unipotent stem cells maintain adult homeostasis in glabrous skin ► Depending on injury mode, each stem cell type responds differently but unipotently ► Sweat duct basal cells and gland myoepithelial cells are multipotent when engrafted ► Sweat and mammary gland stem cells differ in transcription and tissue regeneration Distinct stem cell populations in the sweat gland exhibit different regenerative potential and responses to injury. Progenitors produce de novo sweat glands when engrafted into the breast, revealing fundamental differences between the stem cells that give rise to the sweat and mammary glands and the responsiveness of glandular stem cells to their microenvironment.