Understanding the Molecular Mechanisms of Neuronal Control in Sweat Gland Development

了解汗腺发育中神经元控制的分子机制

• 批准号: 10611450
• 负责人: Juliana Theresa Remark
• 金额: $ 4.43万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10611450
• 关键词: Ablation; Acetylcholine; Affect; Aftercare; Binding; Body Temperature; Brain Injuries; Burn injury; Calcium; Calcium Signaling; Cell Maintenance; Cells; Cessation of life; Chemicals; Data; Defect; Denervation; Dermis; Designer Drugs; Development; Down-Regulation; Duct (organ) structure; Eccrine Glands; Equilibrium; Gene Expression; Genetic Transcription; Gland; Heat Stroke; Homeostasis; Human; Hyperthermia; Image; Knock-in Mouse; Knock-out; Knockout Mice; Maintenance; Mediating; Modeling; Molecular; Morphogenesis; Morphology; Multipotent Stem Cells; Mus; Muscarinic Acetylcholine Receptor M3; Natural regeneration; Nature; Nerve; Neurons; Neurotoxins; Neurotransmitter Receptor; Neurotransmitters; Norepinephrine; Organ failure; Oxidopamine; Pathway interactions; Patients; Phenotype; Physiologic Thermoregulation; Proliferating; Pump; Role; Sarcoplasmic Reticulum; Signal Transduction; Skin; Skin Tissue; Stains; Sweat Glands; Sweat test; Sweating; System; Three-Dimensional Imaging; Water; Work; beta-2 Adrenergic Receptors; cell type; cholinergic; experimental study; gland development; insight; nerve supply; neurotransmission; noradrenergic; progenitor; receptor; receptor expression; regenerative therapy; sarcolipin; severe burns; single-cell RNA sequencing; stem cell differentiation; stem cells; transcriptome; transcriptome sequencing

PROJECT SUMMARY Eccrine sweat glands are the most abundant gland in our skin and are essential for thermoregulation and skin homeostasis. It was only recently that multipotent stem cells in the sweat glands were identified, which presented great potential for de novo sweat gland regeneration. Further, in order to make sweat glands functional, precise innervation and neuronal control are indispensable. Neuronal signals elicit sweating; but also, are necessary for sweat gland maturation based on prior work in our lab. Sweat glands and neurons rely on each other for proper development; however, very little is known about how neuronal inputs influence sweat gland development, especially the sweat gland stem cells. We hypothesize that neuronal innervation is critical for the maintenance of sweat gland stem cells during development. Using mouse sweat gland as a model, we will investigate the molecular changes in the sweat gland stem cells during development when lacking innervation, and further identify the downstream pathway within sweat gland stem cells that mediates the effect of neurotransmitters upon stem cell maintenance. This proposal aims to i) investigate the effect of neuronal input during sweat gland development ii) understand the role of neurotransmitters in sweat gland development iii) examine whether calcium mediates neuronal control of the sweat gland stem cells. These studies will provide greater insight into how nerves regulate the development and maintenance of sweat glands. Further, this proposal will establish a foundational understanding of how sweat glands and neurons develop into a function unit which will be useful for regenerative therapies.

项目概要 小汗腺是我们皮肤中最丰富的腺体，对于体温调节至关重要 和皮肤稳态。直到最近才鉴定出汗腺中的多能干细胞， 这为汗腺从头再生提供了巨大的潜力。此外，为了使汗腺 功能性、精确的神经支配和神经元控制是不可或缺的。神经元信号引发出汗；但 根据我们实验室之前的工作，这也是汗腺成熟所必需的。汗腺和神经元依赖 相互促进，以实现适当的发展；然而，我们对神经元输入如何影响汗水知之甚少 腺体发育，尤其是汗腺干细胞。我们假设神经元的神经支配是 对于发育过程中汗腺干细胞的维持至关重要。使用小鼠汗腺作为 一个模型，我们将研究汗腺干细胞在发育过程中的分子变化 缺乏神经支配，并进一步确定汗腺干细胞内介导的下游途径 神经递质对干细胞维持的影响。该提案旨在 i) 调查以下效果： 汗腺发育过程中的神经元输入 ii) 了解神经递质在汗腺中的作用 iii) 检查钙是否介导汗腺干细胞的神经元控制。这些 研究将更深入地了解神经如何调节汗液的发育和维持 腺体。此外，该提案将为汗腺和神经元如何 发展成为可用于再生疗法的功能单位。