Molecular Mechanisms in Sweat Gland Development

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PROJECT SUMMARY Eccrine sweat glands are the most abundant gland in human skin and are essential for thermoregulation. Human patients suffering from severe burns and sweating deficiency lose their ability to regulate body temperature, which make sweat gland regeneration a critical and immediate next goal in stem cell therapeutics. However, very little is known about the molecular mechanisms involved in the sweat gland development and the regulation of the epidermal progenitors that give rise to sweat glands. This proposal is built upon my previous work on the identification of multipotent stem cells in the sweat glands and the molecular signaling events that specify the sweat gland fate. Using the novel strategies that I had established to study sweat glands, I aim to investigate the mechanical and signaling pathways that further shaped the morphogenesis of sweat duct and gland, with a combination of technologies including microengineering technologies, mouse genetics, immunofluorescent confocal and light sheet microscopy imaging, single cell RNA- and ATAC-sequencing, Fluorescent Activated Cell Sorting, and tissue explant and cell culture systems. This proposed research plans upon completion will provide significant insights into spatiotemporal control of the signaling environment for epidermal progenitor to specify their cell fate of duct vs gland during development. Our studies will significantly impact on the field of sweat gland biology and facilitate the development of novel strategies for future sweat gland regeneration for patients in need.