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: 10402800
• 负责人: Juliana Theresa Remark
• 金额: $ 4.34万
• 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/10402800
• 关键词: 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; Foundations; Gene Expression; Genetic Transcription; Gland; Heat Stroke; Homeostasis; Human; Hyperthermia; Image; Knock-out; Knockout Mice; Lead; 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; Pump; Role; Sarcoplasmic Reticulum; Signal Transduction; Skin; Skin Tissue; Stains; Sweat Glands; Sweat test; Sweating; System; Three-Dimensional Imaging; Water; Work; base; beta-2 Adrenergic Receptors; cell type; cholinergic; designer receptors exclusively activated by designer drugs; 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.

项目摘要 外泌汗腺是我们皮肤中最丰富的腺体，对体温调节至关重要 和皮肤稳态。直到最近，汗腺中的多能干细胞才被发现， 这为从头汗腺再生提供了巨大的潜力。此外，为了使汗腺 功能性的、精确的神经支配和神经元控制是必不可少的。神经元信号引起出汗;但是 根据我们实验室先前的工作，也是汗腺成熟所必需的。汗腺和神经元依靠 然而，关于神经元输入如何影响汗液的知之甚少。 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 在发育过程中对维持汗腺干细胞至关重要。以小鼠的汗腺作为 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的下游通路，介导 神经递质对干细胞维持的影响。本建议旨在i）调查 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 研究将提供更深入的了解神经如何调节汗液的发展和维持 腺体此外，这项建议将建立一个基本的了解如何汗腺和神经元 发展成一个功能单位，这将是有用的再生疗法。