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.

抽象的血液和皮肤等高度再生的组织可以利用血管作为双重参与者组织生长功能：一是供应氧气/营养物，二是调节组织干细胞通过信号传导进行活动。相关证据表明皮肤内皮细胞可能充当向成体毛囊干细胞（HFSC）发出信号，调节其静止状态。到为了证明这一点，我们需要内皮细胞中信号分子的基因靶向，进而会影响干细胞活性。此外，最近关于皮肤血管系统的研究探讨了在成人 HFSC 激活中，淋巴管而非血管。最后是皮肤的程度人们对毛发周期中的脉管系统重塑及其遗传控制知之甚少。我们建议在小鼠中使用遗传和基因组相结合的方法来解决所有这些问题问题。我们的鼠标模型提供了一个令人兴奋的切入点来解决跨领域问题 HFSCs 与邻近内皮细胞的通讯，以探究其生理功能相关性，并首次将内皮细胞作为成人真正的信号传导生态位 HFSC。这项工作未来将对人类皮肤再生研究和更深入地了解皮肤血管疾病。