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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：
7348400
负责人：
ELAINE FUCHS
金额：
$ 37.21万
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 2009-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7348400
关键词：
Address Adopted Adult Animals Basal Cell Biochemical Burn injury Cells Cellular biology Characteristics Clinical Complex Condition Cues DNA-Binding Proteins Dermal Development Embryo Embryonic Development Engineering Engraftment Epidermis Epithelial Epithelium Exhibits Extracellular Matrix Gene Expression Genes Green Fluorescent Proteins Growth Factor Hair Hair Cells Hair follicle structure Histones Homeostasis Hormonal Hormones Hospitals Human In Vitro Injury Integrins Keratin-19 Knock-out Knowledge Label Left Maintenance Malignant Neoplasms Modeling Molecular Multipotent Stem Cells Mus Natural regeneration Nutrient ORALIT Patients Pattern Physiologic pulse Plant Roots Population Property Proteins Pulse taking Purpose Research Sebaceous Glands Skin Stem cells Stimulus Stress Tetanus Helper Peptide Therapeutic Thinking Tissues Totipotent Stem Cells Transgenic Mice Transgenic Organisms Work Wound Healing adult stem cell base cell cortex clinical application cytokine embryonic stem cell human disease in vivo insight keratinocyte novel strategies programs promoter research study response response to injury stem stem cell technology tissue regeneration tongue papilla trauma units tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): Stem cells are natural units of tissue repair and homeostasis. Recent studies suggest that stem cells may be more versatile than previously appreciated. This property holds promise for tissue regeneration, particularly for less controversial adult stem cells. Our global objective is to develop strategies for the isolation, purification and characterization of multipotent adult skin stem cells and their transitamplifying progeny. While skin keratinocytes are one of the few adult stem cells that can be maintained and propagated in vitro, their identification and isolation have been hampered by the lack of reliable markers that distinguish stem cells from their progeny. Without this information, the stress of removing stem cells from their niche make it impossible to assess at what point these cells might cease to function as multipotent stem cells. Here, we propose a novel strategy for purification of multipotent adult murine skin stem cells from their natural niche, by taking advantage of the slow-cycling properties and the few known markers preferentially expressed in these cells. We also devise strategies for purifying three different transit-amplifying progeny of these cells. We will determine and compare the global expression patterns of these cell populations and employ these and known markers to examine how skin stem cells change programs of gene expression during both embryonic development, and postnatally, in natural homeostasis, with the hair cycle, in response to injury or tumorigenesis, and when placed in culture. Finally, we will use this information to explore the functional consequences of altering the expression programs of key genes, which distinguish skin stem cells from their non-stem lineages. Taken together, these studies are expected to provide new and important insights into understanding how skin stem cells possess and maintain their unique self-renewing properties, and how they adopt different fates, including epidermal and hair follicle differentiation. This research is a fundamental prerequisite to ascertaining the potential of skin stem cells for therapeutic purposes that go beyond their present use in providing long-term engraftment on burn patients.

描述（由申请人提供）：干细胞是组织修复和体内平衡的天然单位。最近的研究表明，干细胞可能比以前想象的更通用。这一特性为组织再生带来了希望，特别是对于争议较少的成体干细胞。我们的全球目标是制定多能成体皮肤干细胞及其转运扩增后代的分离、纯化和表征策略。虽然皮肤角质形成细胞是少数可以在体外维持和繁殖的成体干细胞之一，但由于缺乏区分干细胞与其后代的可靠标记物，它们的识别和分离受到阻碍。如果没有这些信息，将干细胞从其生态位中移除的压力使得无法评估这些细胞在什么时候可能停止作为多能干细胞发挥作用。在这里，我们提出了一种新的策略，通过利用慢循环特性和在这些细胞中优先表达的少数已知标记物，从其自然生态位中纯化多能成年鼠皮肤干细胞。我们还设计了纯化这些细胞的三种不同转运放大后代的策略。我们将确定和比较这些细胞群的整体表达模式，并利用这些和已知的标记来检查皮肤干细胞在胚胎发育和出生后、自然稳态、毛发周期、响应损伤或肿瘤发生以及置于培养物中如何改变基因表达程序。最后，我们将利用这些信息来探索改变关键基因表达程序的功能后果，这些基因将皮肤干细胞与其非干细胞谱系区分开来。总而言之，这些研究有望为了解皮肤干细胞如何拥有和维持其独特的自我更新特性，以及它们如何采取不同的命运（包括表皮和毛囊分化）提供新的重要见解。这项研究是确定皮肤干细胞治疗用途潜力的基本先决条件，其治疗用途超出了其目前在烧伤患者身上提供长期移植的用途。