Regulatory Functions of the Differentiated Epidermis

分化表皮的调节功能

• 批准号: 10620771
• 负责人: Terry H Lechler
• 金额: $ 45.37万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-15 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10620771
• 关键词: Ablation; Adherens Junction; Architecture; Automobile Driving; Back; Basement membrane; Behavior; Cell Adhesion; Cell Count; Cell Differentiation process; Cells; Chemicals; Collaborations; Communication; Coupling; Data; Daughter; Dermis; Development; Disease; Embryonic Development; Ensure; Environmental Risk Factor; Epidermis; Family; Feeds; Functional disorder; Genetic; Goals; Mechanics; Parents; Pathway interactions; Play; Population; Proliferating; Proteins; Publishing; Regulation; Role; Signal Transduction; Skin; Skin Physiology; Structure; Testing; Thick; Tissues; Work; Wound healing therapy; cell behavior; cell type; daughter cell; embryonic stem cell; epidermal stem cell; epidermis cell; gene function; loss of function; mechanical drive; migration; mouse model; novel; offspring; protein function; regeneration potential; regenerative biology; regenerative cell; regenerative therapy; regenerative treatment; response; skin barrier; skin organogenesis; stem cell biology; stem cell niche; stem cell proliferation; stem cells; tool; transcription factor

Abstract The epidermis forms an essential barrier to the outside world. To accomplish this, it contains proliferative stem cells that replenish the tissue, giving rise to differentiated cells that form a functional barrier. We have found that the differentiated cells of the epidermis play an important role in regulating the behavior of their parental stem cells, making them not only descents of the stem cells but part of their regulatory niche. Moreover, the mechanical status of differentiated cells, namely their contractility, is a strong input into multiple aspects of epidermal stem cell behavior, including proliferation, migration, and cell fate decisions. Here we seek to define the pathways, both mechanical and chemical, by which differentiated epidermal cells control both stem cell behavior and skin physiology. Defining the niche components and the mechanisms by which they influence epidermal stem cell behavior is essential to allow manipulation of stem cells for regenerative therapies and/or treatment of diseases that result from stem cell dysregulation.

抽象的 表皮形成了与外界的重要屏障。为了实现这一点，它包含 增殖干细胞补充组织，产生分化细胞，形成 功能性屏障。我们发现表皮的分化细胞起着重要的作用 在调节其亲本干细胞的行为中发挥作用，使它们不仅是 干细胞但其监管生态位的一部分。此外，差异化的机械状态 细胞，即它们的收缩性，是表皮干细胞多个方面的强大输入 行为，包括增殖、迁移和细胞命运决定。在这里我们试图定义 机械和化学途径，分化的表皮细胞通过这些途径控制机械和化学途径 干细胞行为和皮肤生理学。定义利基组成部分和机制 它们影响表皮干细胞的行为对于操纵干细胞至关重要 用于再生疗法和/或治疗由干细胞失调引起的疾病。