Molecular Mechanisms in Sweat Gland Development

项目摘要 外泌汗腺是人体皮肤中最丰富的腺体，对体温调节至关重要。人类 患有严重烧伤和出汗不足的患者失去了调节体温的能力， 这使得汗腺再生成为干细胞治疗中关键的和直接的下一个目标。然而，在这方面， 关于汗腺发育和调节的分子机制知之甚少， 表皮祖细胞产生汗腺。这个建议是建立在我以前的工作， 识别汗腺中的多能干细胞和指定多能干细胞的分子信号传导事件。 汗腺的命运使用我已经建立的研究汗腺的新策略，我的目标是研究 机械和信号通路，进一步塑造了汗腺导管和腺体的形态发生， 包括微工程技术、小鼠遗传学、免疫荧光 共聚焦和光片显微镜成像，单细胞RNA和ATAC测序，荧光激活 细胞分选、组织外植体和细胞培养系统。这项拟议的研究计划完成后， 为表皮祖细胞的信号环境的时空控制提供了重要的见解， 说明了它们在发育过程中导管与腺体细胞命运。我们的研究将对该领域产生重大影响。 汗腺生物学和促进未来汗腺再生的新策略的发展， 病人需要。

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.