The role of P16Ink4a in adult skeletal muscle stem cells

P16Ink4a在成体骨骼肌干细胞中的作用

• 批准号: 10470141
• 负责人: Andrew S Brack
• 金额: $ 43.74万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 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/10470141
• 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; Light; Malignant Neoplasms; Measures; Mechanics; Mediating; Molecular; Mus; Muscle; Muscle satellite cell; Myoblasts; Pharmacology; 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; base; cell motility; extracellular; genetic approach; in vivo; insight; mechanotransduction; migration; novel; receptor; regenerative; repaired; response; response to injury; satellite cell; self-renewal; senescence; stem cell function; stem cells; tissue regeneration; tissue repair

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.

项目总结 细胞迁移、增殖和细胞命运决定的协调对干细胞功能和组织至关重要 修理。我们已经确定经典的促衰老和衰老调节因子p16INK4a参与了 健康成人肌肉干细胞的调控。我们发现p16INK4a在细胞迁移和细胞命运决定中发挥作用 通过细胞骨架和收缩机械。此前还没有报道过这一点。长期目标是 了解p16INK4a是如何诱导和调节非老年健康祖细胞的细胞骨架功能的 纸巾。第一个目标将结合时间调节和细胞特定的遗传策略来确定 P16INK4a在健康成人肌肉干细胞中的表达。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在细胞自主调节自身微环境中的作用。理解p16INK4a的作用 在祖细胞功能方面将导致对衰老、衰老、癌症和肌肉退行性变的重要见解 疾病。