Identifying bio-markers for putative epidermal stem cells in mouse skin.

识别小鼠皮肤中假定的表皮干细胞的生物标志物。

基本信息

批准号：
8827677
负责人：
Tudorita Tumbar
金额：
$ 17.71万
依托单位：
CORNELL UNIVERSITY
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 2017-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8827677
关键词：
Address Adult Aging Alleles Basal Cell Basic Science Biochemical Biological Assay Biological Models Cell Cycle Cell Lineage Cell Therapy Cell Transplantation Cell division Cell model Cell surface Cells Characteristics DNA DNA Sequence Alteration Data Disease Epidermis Epithelium Fluorescence-Activated Cell Sorting Future Gene Expression Profile Genes Genetic Genetic Models Genome Hair follicle structure Health Heterogeneity Histones Homeostasis Human In Situ Hybridization In Vitro Injury Interleukin Receptor Intestines Knock-in Mouse Label Life Link Maps Messenger RNA Microarray Analysis Modeling Molecular Molecular Profiling Mus Mutant Strains Mice Natural regeneration Nature Normal tissue morphology Pathway interactions Pattern Play Population Proliferating Property Regulation Reporting Rest Role Sebaceous Glands Skin Sorting - Cell Movement Stem cells Stratum Basale Study models System Testing Tetanus Helper Peptide Tissues Transgenic Mice Translating Transplantation Wild Type Mouse Work appendage base cell behavior daughter cell differential expression human disease in vitro Assay in vivo injury and repair mathematical model molecular marker novel prevent receptor expression regenerative repaired research study self-renewal skin disorder skin regeneration stem stem cell population stemness tool tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): The infrequently dividing or so-called "slow-cycling" nature of cells within tissues has been linked to stemness in several adult tissues including mouse skin. Slow-cycling cells defined as H2B-GFP or DNA label retaining cells (LRCs) are thought to reside at the top of the lineage hierarchy, as stem cells, giving rise to actively-cyclig cells (non-LRCs), which may function as transit-amplifying (TA) short-lived progenitor cells. Despite the crucial importance of the epidermis for essential body functions and for skin regeneration therapy, molecular characterization of stem and TA cells within the basal layer of the inter-follicular epidermis has not been achieved. Consequently, we lack the specific markers to accurately define the dynamic stem cell behavior within this tissue and to understand the regulatory factors maintaining stemness. In our preliminary study, we have isolated LRCs and non-LRCs from the basal layer of the epidermis and analyzed the molecular signature of these cells by microarray. Here we propose to characterize the expression pattern of several putative epidermal stem and TA cell markers identified in our microarray, including one novel cell surface marker for basal layer LRCs. We will analyze the lineage potential of subpopulations of basal layer cells by three functional assays: colony formation activity, regeneration potential in cell transplantation, and lineage tracing. These data will reveal long-term stem cell potential and lineage hierarchy of epidermal basal cell subpopulations in vitro and in vivo and will provide new tools for studying stem cell regulation in the epidermis. Data obtained from our proposed experiments will have global relevance for stem cell-based therapy of human skin injury or skin replacement, where slow-cycling cells are thought to play central roles.

描述（由申请人提供）：组织内部细胞内的不经常分裂或所谓的“慢循环”性质与包括小鼠皮肤在内的几个成年组织中的干性有关。慢循环细胞定义为H2B-GFP或DNA标记保留细胞（LRC）被认为位于谱系层次结构的顶部，作为干细胞，从而引起活跃的cyclig细胞（非LRCS），这些细胞可能起作用，它们可能充当临床（TA）近距离寿命的近代幼儿园细胞。尽管表皮对于身体功能和皮肤再生疗法的重要性至关重要，但尚未实现炎性表皮基础层内的茎和TA细胞的分子表征。因此，我们缺乏特定的标记来准确定义该组织中的动态干细胞行为，并了解维持干性的调节因素。在我们的初步研究中，我们从表皮的基础层分离了LRC和非LRC，并通过微阵列分析了这些细胞的分子特征。在这里，我们建议表征在微阵列中鉴定出的几个推定表皮茎和TA细胞标记的表达模式，包括基底层LRC的一种新型细胞表面标记。我们将通过三个功能分析来分析基底层细胞亚群的谱系潜力：菌落形成活性，细胞移植中的再生潜力和谱系追踪。这些数据将揭示表皮基底细胞亚群体体外和体内的长期干细胞潜力和谱系层次结构，并将为研究表皮中的干细胞调节提供新的工具。从我们提出的实验中获得的数据将与基于干细胞的人体皮肤损伤或皮肤替代的基于干细胞的治疗具有全球相关性，在该治疗中，人们认为慢速循环细胞起着核心作用。