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。

• 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
• 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

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）：组织内细胞的不频繁分裂或所谓的“慢循环”性质与包括小鼠皮肤在内的几种成人组织的干性有关。被定义为H2B-GFP或DNA标签保留细胞（lrc）的慢循环细胞被认为位于谱系层级的顶端，作为干细胞，产生活跃循环细胞（非lrc），其可能作为转运扩增（TA）短寿命祖细胞。尽管表皮对人体基本功能和皮肤再生治疗至关重要，但尚未实现毛囊间表皮基底层的干细胞和TA细胞的分子表征。因此，我们缺乏特定的标记物来准确定义该组织内的动态干细胞行为，并了解维持干细胞性的调节因子。在我们的初步研究中，我们从表皮基底层分离了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，我们提出表征在我们的微阵列中鉴定的几种假定的表皮干和TA细胞标记物的表达模式，包括基底层lrc的一种新的细胞表面标记物。我们将通过三种功能测定来分析基底层细胞亚群的谱系潜力：集落形成活性、细胞移植中的再生潜力和谱系追踪。这些数据将揭示体外和体内表皮基底细胞亚群的长期干细胞潜力和谱系等级，并将为研究表皮干细胞调控提供新的工具。从我们提出的实验中获得的数据将对人类皮肤损伤或皮肤替代的干细胞治疗具有全球相关性，其中慢循环细胞被认为起着核心作用。