Functional characterization of sebaceous gland stem cells and sebocytes in the skin

皮肤皮脂腺干细胞和皮脂腺细胞的功能表征

基本信息

批准号：
10558590
负责人：
Sunny Y Wong
金额：
$ 42.24万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-01 至 2026-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10558590
关键词：
16S ribosomal RNA sequencing Ablation Acne Adult Alopecia Antioxidants Attenuated Biology Candidate Disease Gene Cell Compartmentation Cells Cicatrix Communication Complex Cues Cytometry Data Set Defect Disease Dry Eye Syndromes Epidermal Growth Factor Receptor Epidermis Epithelium Eye diseases Eyelid structure Foundations Genes Gland Goals Growth Factor Hair Hair follicle structure Homeostasis Hormones Hydration status Immune Ligands Link Lipids Morphology Mus Oils Outcome PPAR gamma Pathology Pathway interactions Play Population Proliferating Property Regulation Role Sebaceous Glands Seborrheic dermatitis Sebum Signal Pathway Signal Transduction Skin Source Surface System Testing Time Up-Regulation Water Work antimicrobial antimicrobial drug appendage cytokine epigen experimental study keratin 5 lipidomics meibomian gland microbiome research mutant notch protein novel progenitor receptor skin barrier skin disorder stem cell differentiation stem cells transcription factor transcriptome sequencing

项目摘要

Project Summary / Abstract Normal skin function is thought to depend on sebaceous glands (SGs), which are paired appendages typically associated with hair follicles. The main purpose of SGs is to secrete sebum, a lipid-rich substance that acts on the skin to regulate barrier function and hydration, while possibly possessing anti-oxidant and anti-microbial properties. Aberrant SGs have been associated with skin pathologies such as acne and scarring alopecia, but their functional roles in disease remain unclear. Although numerous genes and signaling pathways have been implicated in maintaining SGs, few studies have characterized the mechanisms by which these factors modulate SG stem cell differentiation, and whether their effects are direct or indirect. Our previous studies have found that Notch signaling simultaneously exerts dual opposing effects on SGs: Whereas Notch directly promotes SG stem cell differentiation, this pathway also indirectly suppresses SGs by regulating proper differentiation in the surface interfollicular epidermis. We further observed that a PPARγ/K5 double-positive population likely serves as the immediate progenitors that give rise to differentiated sebocytes in the gland. This proposal seeks to identify some of the complex factors that regulate SG stem cells and to test the requirement for SGs in maintaining normal skin function. In Aim 1, we will examine how Notch directly promotes SG stem cell differentiation, and evaluate novel genes that may modulate SG function. In Aim 2, we will determine how disruption of Notch-dependent epidermal differentiation causes SGs to enlarge. In Aim 3, we will assess the consequences of deleting SGs throughout the skin. Altogether, these studies will characterize how SG stem cells are regulated, both locally and from a distance, and potentially uncover novel functions for these glands. These studies build upon the emerging concept that different cellular sub- compartments in the skin are intricately linked and communicate with each other through a variety of signaling cues.

项目概要/摘要人们认为正常的皮肤功能取决于皮脂腺 (SG)，皮脂腺通常是成对的附属物 SG 的主要作用是分泌皮脂，这是一种作用于毛囊的富含脂质的物质。皮肤调节屏障功能和水合作用，同时可能具有抗氧化和抗菌作用异常的 SG 与痤疮和疤痕性脱发等皮肤病有关。它们在疾病中的功能作用仍不清楚。尽管许多基因和信号通路与维持 SG 相关，但很少有研究表明表征了这些因子调节 SG 干细胞分化的机制，以及它们是否我们之前的研究发现Notch信号同时发挥双重作用。对 SG 的相反作用：尤其是 Notch 直接促进 SG 干细胞分化，该途径也通过调节表面滤泡间表皮的适当分化来间接抑制 SG。进一步观察到 PPARγ/K5 双阳性群体可能是在腺体中产生分化的皮脂细胞。该提案旨在确定一些调节 SG 干细胞的复杂因素并测试 SG 维持正常皮肤功能的要求在目标 1 中，我们将直接研究 Notch 的作用。促进 SG 干细胞分化，并评估可能调节 SG 功能的新基因。将决定 Notch 依赖性表皮分化的破坏如何导致 SG 增大。在目标 3 中，我们将评估删除整个皮肤 SG 的后果，这些研究将共同评估。描述 SG 干细胞如何在本地和远程进行调节，并有可能发现新的这些研究建立在不同细胞亚群的新兴概念之上。皮肤中的隔室错综复杂地连接在一起，并通过各种信号传导相互通信提示。