The role of P16Ink4a in adult skeletal muscle stem cells

P16Ink4a在成体骨骼肌干细胞中的作用

基本信息

批准号：
10661698
负责人：
Brian Feeley
金额：
$ 44.53万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-17 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10661698
关键词：
Adhesions Adult Aging Atomic Force Microscopy Behavior Biomechanics Biomedical Engineering CDKN2A gene Cell Adhesion Cell physiology Cells Complex Cytoskeleton Data Degenerative Disorder Disease Environment Extracellular Matrix Feedback Fibronectins Genetic Goals Heterogeneity Image In Vitro Integrins Knock-out Malignant Neoplasms Measures Mechanics Mediating Molecular Mus Muscle Muscle satellite cell Myoblasts Phenotype Play Process Proliferating Property Publishing Regenerative capacity Regulation Reporter Reporting Role Sampling Series Signal Transduction Skeletal Muscle Testing Time Tissues Traction Force Microscopy Trauma Tumor Suppressor Proteins Work adult stem cell cell motility extracellular genetic approach in vivo insight mechanotransduction migration novel pharmacologic receptor regenerative repaired response response to injury satellite cell self-renewal senescence stem cell function stem cells tissue regeneration tissue repair transmission process

项目摘要

PROJECT SUMMARY Coordination of cell migration, proliferation and cell fate determination is critical for stem cell function and tissue repair. We have identified that P16Ink4a, the classic pro-senescence and aging regulator, participates in the regulation of healthy adult muscle stem cells. We find a role for P16Ink4a in cell migration and cell fate decisions via the cytoskeleton and contractile machinery. This has not been reported previously. The long-term goal is to understand how P16Ink4a is induced and regulates cytoskeletal function of healthy progenitor cells in non-aged tissues. The first aim will combine temporal regulated and cell specific genetic strategies to determine the role of P16Ink4a in healthy adult muscle stem cells. The second aim will dissect the functional and molecular mechanism that regulates cell mechanics, migration and cell fate via P16Ink4a. The third aim will examine the role of P16Ink4a in cell autonomous regulation of its own microenvironment. Understanding the role of P16Ink4a in progenitor cell function will lead to important insights for aging, senescence, cancer and muscle degenerative diseases.

项目概要细胞迁移、增殖和细胞命运决定的协调对于干细胞功能和组织至关重要维修。我们已经确定，经典的促衰老和衰老调节因子 P16Ink4a 参与健康成人肌肉干细胞的调节。我们发现 P16Ink4a 在细胞迁移和细胞命运决定中的作用通过细胞骨架和收缩机制。此前尚未报道过这一情况。长期目标是了解 P16Ink4a 如何被诱导并调节非衰老健康祖细胞的细胞骨架功能组织。第一个目标将结合时间调节和细胞特异性遗传策略来确定健康成人肌肉干细胞中的 P16Ink4a。第二个目标将剖析功能和分子通过 P16Ink4a 调节细胞力学、迁移和细胞命运的机制。第三个目标将审查 P16Ink4a 在细胞自主调节其自身微环境中的作用。了解 P16Ink4a 的作用对祖细胞功能的研究将为衰老、衰老、癌症和肌肉退化提供重要见解疾病。