Skin Stem Cells: Purification and Characterization

皮肤干细胞：纯化和表征

基本信息

批准号：
10407470
负责人：
ELAINE FUCHS
金额：
$ 36.92万
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/10407470
关键词：
Address Age Aging Apoptosis Behavior Biology Cell Lineage Cells Cessation of life ChIP-seq Disease Embryo Engraftment Environment Epithelial 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 Sweat Glands Testing Time Tissues Work adult stem cell age related burn therapy cell behavior cell injury 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 function stem cell niche stem cell population stem cell survival stem cells tissue regeneration tissue repair transcriptome 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全球目标是阐明组织稳态和哺乳动物皮肤的再生，了解该过程如何在人类疾病中出现问题，包括癌症。实现这一目标的核心是皮肤内不同干细胞（SC）的表征，确定其对组织内稳态和伤口修复的相对贡献，并阐明如何变化在利基市场中，微环境会影响这些事件。过去的AR050452研究导致毛囊纯化（HF）凸起和基本的嗜热表皮（EPD）细胞，并建立了长期寿命的自我更新 SC在组织再生和伤口修复中起作用。但是，在其生物学和组织中再生任务，这些SC显示出不同的行为，这些行为似乎是在其独特的微环境（利基）。该领域仍然缺乏对这些壁ni的构成的全面知识， SC的性质：利基相互作用及其如何帮助干细胞应对压力的情况。过去的AR050452 研究为解决以下关键问题的基础设定了基础：（1）。哪些利基组件是什么 HFSC的以及它们如何随着头发周期而变化？（2）EPD和HF-的相对贡献是什么 SC赢得维修？浅表与深度胜利的差异是否有差异？在年轻的老鼠中？（3）什么是响应伤害和衰老而发生的SC-niche串扰的变化以及它们的生理是什么关联？（4）SC在其利基障碍中如何应对并协调当地违规行为的修复？哪个细胞向周围的免疫细胞传递损伤信号，如何触发它们？怎么办 SCS生存？（5）当大部分HF经历时，SC在头发周期结束时如何保护自己细胞凋亡和末端分化？要回答这些问题，我们将使用FACS，单细胞RNA-seq，芯片 - SEQ，条件基因敲除和RNAi在体内筛选，并采用这些方法探索皮肤干细胞在其本地，突变和伤口引起的环境中。