Molecular Mechanisms in Sweat Gland Development

汗腺发育的分子机制

基本信息

批准号：
10660583
负责人：
Catherine Pei-Ju Lu
金额：
$ 55.19万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-01 至 2028-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10660583
关键词：
ATAC-seq Affect Biology Biomedical Engineering Body Temperature Brain Injuries Burn injury Cell Culture System Cell Separation Cells Cessation of life Collagen Cues Data Dermal Dermis Development Developmental Biology Developmental Process Duct (organ) structure Eccrine Glands Engineering Environment Equilibrium Event Fibroblasts Future Gland Glandular Cell Goals Heat Stroke Human Hyperthermia Knock-out Knockout Mice Knowledge Lead Length Ligands Light Mechanics Methods Molecular Morphogenesis Multipotent Stem Cells Mus Natural regeneration Organ failure Patients Pattern Physiologic Thermoregulation Piezo 1 ion channel Regulation Research Research Proposals Role Shapes Signal Pathway Signal Transduction Signaling Molecule Skin Specific qualifier value Sweat Glands Sweating Technology Testing Tissue Engineering Tissues WNT Signaling Pathway Water Work cell fate specification conditional knockout design epidermal stem cell experimental study gland development innovation insight keratinocyte mechanical force microfluidic technology microscopic imaging mouse genetics mouse model notch protein novel novel strategies overexpression progenitor response severe burns single-cell RNA sequencing skin regeneration spatiotemporal stem cell biology stem cell therapy stem cells

项目摘要

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.

项目概要小汗腺是人体皮肤中最丰富的腺体，对于体温调节至关重要。人类严重烧伤和出汗不足的患者失去调节体温的能力，这使得汗腺再生成为干细胞治疗中关键且迫在眉睫的下一个目标。然而，关于汗腺发育和调节所涉及的分子机制知之甚少产生汗腺的表皮祖细胞。这个建议是建立在我之前的工作基础上的汗腺中多能干细胞的鉴定以及指定汗腺的分子信号事件汗腺的命运。使用我为研究汗腺而建立的新策略，我的目标是研究机械和信号通路进一步塑造了汗管和腺体的形态发生，微工程技术、小鼠遗传学、免疫荧光等技术组合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将为表皮祖细胞信号传导环境的时空控制提供重要见解指定它们在发育过程中导管与腺体的细胞命运。我们的研究将对以下领域产生重大影响汗腺生物学并促进未来汗腺再生新策略的开发有需要的患者。