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

• 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
• 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

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.

项目摘要 /摘要 正常的皮肤功能被认为取决于皮脂腺（SG），通常是配对的附属物 与毛囊有关。 SGS的主要目的是Secret Secbum，一种作用于脂质的物质的物质 皮肤调节屏障功能和水合，同时具有抗氧化剂和抗微生物 特性。异常的SG与皮肤病理学有关 它们在疾病中的功能作用尚不清楚。 尽管在维持SG中隐含了许多基因和信号通路，但很少有研究 这些因素调节了SG干细胞分化的机制，以及它们是否是否 效果是直接或间接的。我们以前的研究发现Notch信号只是导出双重 对SGS的相反影响：虽然Notch直接促进了SG干细胞分化，但此途径也 通过调节表面互眼表皮中的适当分化来间接抑制SG。我们 进一步观察到，PPARγ/K5双阳性种群可能是直接的祖细胞， 引起腺体中分化的皮脂细胞。 该建议旨在确定调节SG干细胞并测试的一些复杂因素 SGS维持正常皮肤功能的要求。在AIM 1中，我们将研究直接的缺口 促进SG干细胞分化，并评估可能调节SG功能的新型基因。在AIM 2中，我们 将确定Notch依赖性表皮分化的破坏导致SGS扩大。在AIM 3中， 我们将评估在整个皮肤中删除SGS的后果。这些研究总共 表征了SG干细胞如何调节本地和远处的调节，并可能发现新颖的 这些腺体的功能。这些研究以不同的细胞亚概念为基础 皮肤中的隔室复杂地连接并通过多种信号相互通信 提示。