Interfollicular epidermal stem cells in human and mouse skin

人和小鼠皮肤中的滤泡间表皮干细胞

• 批准号: 8149973
• 负责人: GEORGE COTSARELIS
• 金额: $ 17.28万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-23 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8149973
• 关键词: Abdomen; Address; Adult; Aging; Alopecia; Area; Attention; Biological Assay; Biology; Burn injury; Cells; Chronic; Cutaneous; Data; Dermis; Epidermis; Epithelial; Epithelium; Gene Expression; Genes; Genetic; Goals; Hair; Hair follicle structure; Hematopoietic; Human; In Vitro; Integrin alpha6; LacZ Genes; Malignant Neoplasms; Modeling; Molecular Profiling; Mus; Natural regeneration; Neonatal; Physiologic pulse; Population; Production; Protocols documentation; Research; Role; Skin; Skin Aging; Stem cells; Stratum Basale; Structure; System; T-cell acute lymphocytic leukemia 1 protein; Tamoxifen; Techniques; Testing; Therapeutic; Time; Tissues; design; fetal; in vitro Model; in vivo; keratinocyte; mouse model; multipotent cell; new technology; novel; novel strategies; penis foreskin; postnatal; postnatal human; prominin; public health relevance; reconstitution; regenerative; relating to nervous system; research study; response; self-renewal; skin regeneration; stem cell biology; stem cell population; tool

DESCRIPTION (provided by applicant): Adult somatic stem cells are thought to be responsible for the continued self renewal of the epidermis. Although hair follicle stem cells in the bulge have been well characterized, our understanding of stem cells in the interfollicular epidermis remains poor. We have discovered unique cells within human and mouse postnatal skin which co-express the stem cell marker CD133 and basal marker alpha6 integrin. Our preliminary studies indicate that these cells exist in discrete patches within interfollicular basal epithelium, express stem cell genes such as nanog and achaete scute-like 3 and may generate new hair follicles in in vivo reconstitution ("patch") assays. We postulate that these cells are true multipotent interfollicular stem cells, capable of self renewal and the regeneration of skin components, specifically epidermis and hair follicles. We will use human and mouse models to test this hypothesis. The discovery of an interfollicular stem cell population with multipotent capability would have high impact on skin biology, challenging current models of skin and HF regeneration, and provide a powerful new tool for therapeutic treatment of chronic wounds and alopecia. PUBLIC HEALTH RELEVANCE: We will study stem cells in the outer portion of the skin called the epidermis. The goal is to better understand the cells responsible for the constant production of this layer and its remarkable response to wounding. Ultimately, this research may impact on developing new treatments for skin problems such as chronic wounds, burns, alopecia and skin aging.

描述(申请人提供)：成体干细胞被认为负责表皮的持续自我更新。虽然对毛囊隆起中的毛囊干细胞已经有了很好的描述，但我们对毛囊间表皮中的干细胞的了解仍然很少。我们在人类和小鼠出生后的皮肤中发现了独特的细胞，它们共同表达干细胞标记CD133和基础标记α6整合素。我们的初步研究表明，这些细胞存在于毛囊间基底上皮内的离散斑块中，表达干细胞基因，如nanog和achaete scute-like 3，并可能在体内重建实验中生成新的毛囊。我们推测这些细胞是真正的多能毛囊间干细胞，能够自我更新和皮肤成分的再生，特别是表皮和毛囊。我们将使用人类和老鼠模型来检验这一假设。具有多能能力的毛囊间干细胞的发现将对皮肤生物学产生重大影响，挑战现有的皮肤和HF再生模型，并为慢性伤口和脱发的治疗提供强有力的新工具。 与公共卫生相关：我们将研究皮肤外部称为表皮的干细胞。目的是为了更好地了解负责这一层的持续产生及其对创伤的显着反应的细胞。最终，这项研究可能会对开发治疗慢性伤口、烧伤、脱发和皮肤老化等皮肤问题的新疗法产生影响。