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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：
10373597
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/10373597
关键词：
16S ribosomal RNA sequencing Acne Adult Alopecia Antioxidants Attenuated Biology Candidate Disease Gene Cell Compartmentation Cells Cicatrix Complex Cues Cytometry Data Set Defect Disease Dry Eye Syndromes Epidermal Growth Factor Receptor Epidermis Epithelial Eyelid structure Foundations G Cells Genes Gland Goals Growth Factor Hair Hair follicle structure Homeostasis Hormones Hydration status Hypersensitivity skin testing Immune Ligands Link Lipids Morphology Mus Oils Outcome PPAR alpha PPAR gamma Pathology Pathway interactions Play Population Property Regulation Role Sebaceous Gland Diseases 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.

项目摘要/摘要