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Skin Stem Cells: Purification and Characterization

皮肤干细胞：纯化和表征

基本信息

批准号：
10618315
负责人：
ELAINE FUCHS
金额：
$ 37.29万
依托单位：
ROCKEFELLER UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-02-26 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10618315
关键词：
Acceleration Address Age Aging Apoptosis Behavior Biology Cell Lineage Cells Cessation of life ChIP-seq Collaborations Cytoprotection Disease Embryo Engraftment Environment Epithelium Event Fluorescent in Situ Hybridization Foundations Genetic Genetic Diseases Goals Hair Hair follicle structure Homeostasis Human Immune Immunofluorescence Immunologic Inflammatory Injury Knowledge Malignant Neoplasms Methods Modeling Molecular Morphogenesis Mus Natural regeneration Nature Normal tissue morphology Organism Phase Physiological Play Process Proliferating Property RNA interference screen Regenerative Medicine Reporter Research Rest Role Sebaceous Glands Signal Transduction Skin Skin injury Stress Stress and Coping Sweat Glands Testing Tissues Work adult stem cell age related burn therapy cell behavior cell injury coping design epidermis cell epithelial stem cell experience genetic approach improved in vivo innovation insight keratin 5 knockout gene mutant novel novel therapeutics progenitor programs recruit regenerative regenerative therapy regenerative tissue repaired response response to injury self-renewal severe injury single-cell RNA sequencing skin barrier stem cell expansion stem cell function stem cell niche stem cell population stem cell proliferation stem cell survival stem cells tissue regeneration tissue repair transcriptome transmission process tumor wound wound healing wound treatment

项目摘要

Project Summary The global objective of this research is to elucidate the mechanisms underlying tissue homeostasis and regeneration in mammalian skin and to understand how this process goes awry in human disorders, including cancers. Central to achieving this goal is the characterization of the different stem cells (SCs) within skin, determining their relative contributions to tissue homeostasis and wound-repair, and elucidating how changes in niche microenvironments impact these events. Past AR050452 research led to purification of hair follicle (HF) bulge and basal inter-follicular epidermal (Epd) cells, and established them as long-lived, self-renewing SCs that function in tissue regeneration and wound-repair. However, both in their biology and their tissue regenerative tasks, these SCs display distinct behaviors that appear to be predicated on their unique microenvironments (niches). The field still lacks a comprehensive knowledge of the constituents of these niches, the nature of SC:niche interactions, and how they help stem cells cope with stressful situations. Past AR050452 research has set the foundations to tackle the following key questions: (1). What are the niche components of HFSCs and how do they change with the hair cycle? (2) What are the relative contributions of Epd- and HF- SCs to wound repair? Does this differ in superficial vs deep wounds? In young vs aging mice? (3) What are the changes in SC-niche crosstalk that occur in response to injury and aging and what is their physiological relevance? (4) How do SCs respond to and orchestrate the repair of local breaches in their niche barrier? Which cells transmit damage signals to the surrounding immune cells and how are they triggered to do so? How do SCs survive? (5) How do SCs protect themselves at the end of the hair cycle, when the bulk of the HF undergoes apoptosis and terminal differentiation? To answer these questions, we’ll use FACS, single cell RNA-seq, ChIP- seq, conditional gene knockout and RNAi screens in vivo and employ these methods to explore skin stem cells in their native, mutant and wound-induced environments.

项目摘要这项研究的总体目标是阐明组织稳态的机制，哺乳动物皮肤再生，并了解这一过程在人类疾病中如何出错，包括癌的实现这一目标的核心是表征皮肤内的不同干细胞（SC），确定它们对组织稳态和伤口修复的相对贡献，并阐明它们如何改变在生态位微环境影响这些事件。过去的AR 050452研究导致毛囊的纯化 (HF)隆突和基底滤泡间表皮（Epd）细胞，并建立他们作为长寿，自我更新在组织再生和伤口修复中起作用的SC。然而，在它们的生物学和组织中，在再生任务中，这些SC显示出不同的行为，这些行为似乎是基于它们独特的微环境（niches）。该领域仍然缺乏对这些小生境的组成的全面了解， SC的性质：利基相互作用，以及它们如何帮助干细胞科普压力情况。过去的AR 050452 研究为解决以下关键问题奠定了基础：（1）。什么是利基组件以及它们如何随着毛发周期而变化？(2)Epd-和HF-的相对贡献是什么？创伤修复的治疗方法？这是否与浅表和深部伤口不同？在年轻的老鼠和年老的老鼠之间？(3)有哪些 SC-生态位串扰的变化，发生在响应损伤和老化，什么是他们的生理相关性？(4)供应链如何应对和协调修复其生态位屏障中的地方缺口？这细胞将损伤信号传递给周围的免疫细胞，它们是如何被触发这样做的？怎么 SC存活？(5)在毛发周期结束时，当大部分HF经历了凋亡和终末分化？为了回答这些问题，我们将使用FACS，单细胞RNA测序，ChIP- seq、条件性基因敲除和RNAi体内筛选，并利用这些方法探索皮肤干细胞在它们的原生、突变和创伤诱导的环境中。

项目成果

期刊论文数量（30）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Ezh2 orchestrates gene expression for the stepwise differentiation of tissue-specific stem cells.

DOI：
10.1016/j.cell.2008.12.043
发表时间：
2009-03-20
期刊：
Cell
影响因子：
64.5
作者：
Ezhkova E;Pasolli HA;Parker JS;Stokes N;Su IH;Hannon G;Tarakhovsky A;Fuchs E
通讯作者：
Fuchs E

The tortoise and the hair: slow-cycling cells in the stem cell race.