Investigating the coordinated endothelial-epithelial interactions in adult hair cycle of mouse skin

研究小鼠皮肤成年毛发周期中协调的内皮-上皮相互作用

基本信息

批准号：
10674132
负责人：
Tudorita Tumbar
金额：
$ 47.23万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-28 至 2028-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10674132
关键词：
Ablation Address Adult Affect Arteries Attention BMP4 Behavior Blood Blood Vessels Blood capillaries Cell Lineage Cells Cessation of life Communication Data Defect Disease Endothelial Cells Endothelium Epithelial Cells Epithelium Exercise Future Gene Expression Gene Expression Profile Gene Targeting Genetic Genetic study Genomic approach Growth Hair Hair follicle structure Hematopoietic Hereditary hemorrhagic telangiectasia Homeostasis Human Laboratories Lymphatic Maintenance Maps Molecular Morphology Mus Mutation Nutrient Physiological Play Process Proliferating Regenerative research Regulation Role Signal Pathway Signal Transduction Signaling Molecule Skin TGF Beta Signaling Pathway Testing Time Tissues Transforming Growth Factor beta Receptors Veins Work epithelial stem cell experimental study genetic approach human disease intercellular communication lymphatic vessel mouse genetics mouse model neural notch protein novel regenerative tissue skin regeneration stem cell niche stem cells tissue regeneration tissue stem cells

项目摘要

Abstract Highly regenerative tissues such as blood and skin may utilize blood vessels as dual players in tissue growth functions: one in supplying O2/nutrients and another in regulating tissue stem cell activity via signaling. Correlative evidence suggest that skin endothelial cells may act as signaling niches to adult hair follicle stem cells (HFSCs), regulating their quiescence. To demonstrate this, we need gene targeting of signaling molecules in endothelial cells that in turn would affect stem cell activity. Furthermore, recent work on skin vasculature probed a role of lymphatic vessels but not of blood vessels in adult HFSC activation. Finally, the extent of skin vasculature remodeling and its genetic control during the hair cycle are poorly understood. We propose to use a combined genetic and genomic approach in mice to address all these questions. Our mouse models provide an exciting entry point to address the cross- communication of HFSCs with the neighboring endothelial cells, to probe its physiological relevance, and to place endothelial cells for the first time as bona-fide signaling niches for adult HFSCs. This work will have future broad relevance for human skin regeneration studies and for more in depth understanding of skin vasculature disease.

抽象的高度再生组织（例如血液和皮肤）可以利用血管作为双重玩家组织生长功能：一种在供应O2/营养素，另一个用于调节组织干细胞通过信号活动的活动。相关证据表明，皮肤内皮细胞可能充当向成年毛囊干细胞（HFSC）发出信号生态位，调节其静止。到证明这一点，我们需要在内皮细胞中信号分子的基因靶向依次会影响干细胞活性。此外，最近关于皮肤脉管系统的工作探讨了成人HFSC激活中血管的淋巴管，而不是血管。最后，皮肤的程度脉管系统重塑及其在头发周期期间的遗传控制知之甚少。我们建议在小鼠中使用遗传和基因组方法来解决所有这些问题。我们的鼠标模型提供了一个令人兴奋的切入点，以解决交叉 HFSC与相邻内皮细胞的通信，以探测其生理相关性，并首次将内皮细胞作为成人的真正信号壁ch HFSC。这项工作将在人类皮肤再生研究和对皮肤脉管系统疾病的深入了解。