Elucidating the function of a distinct cell population in adult mammalian tendons

肌腱损伤是活跃的个人和老年人的常见问题。虽然是外科手术 干预可恢复力量和活动能力，并发症频发，失败率高等 以及与运动相关的疼痛，经常发生。对分子的更好理解 和调节肌腱组织维持、细胞更新和损伤的细胞机制 反应将具有重大的治疗意义。研究表明，来自 肌腱组织具有干细胞/祖细胞特征，它们被认为有助于 肌腱组织的动态平衡和修复。然而，这些研究是在提取后进行的 以及我们目前对这些细胞在体内行为的了解 在维修和受伤期间的反应非常有限。此外，我们也没有办法 前瞻性地识别、从基因上定位并研究其本国独特的肌腱细胞群 环境。我们建议使用谱系追踪策略来研究细胞周转率，基因 体内唯一基因标记的肌腱细胞亚群的表达和功能特性。 使用这些方法，我们将测试这样的假设，即这个特别标记的子集 肌腱细胞是常驻的肌腱前体细胞，需要特定的途径才能 肌腱愈合反应。对这种独特的细胞群体的了解将影响我们的基础 了解肌腱内细胞类型的多样性，将大大促进我们的 直接分离和基因操作这些细胞的能力。这项工作是至关重要的一步 致力于研究独特的肌腱祖细胞群在它们的自然环境和意志 为未来旨在阐明其调节机制的研究奠定了基础 活动。

Tendon injuries are common problems for active individuals and aging adults. Although surgical intervention can restore strength and mobility, frequent complications, such as a high failure rate and pain associated with movement, often occur. An improved understanding of the molecular and cellular mechanisms regulating tendon tissue maintenance, cell renewal, and injury response would have significant therapeutic implications. Studies have shown that cells from tendon tissues have stem/progenitor cell characteristics, and they are thought to contribute to tendon tissue homeostasis and repair. However, these studies were performed after extraction and expansion in culture, and our current knowledge as to the in vivo behaviors of these cells during maintenance and injury response is very limited. In addition, we have no means to prospectively identify, genetically target, and study unique tendon cell populations in their native environment. We propose to employ lineage tracing strategies to study cell turnover rates, gene expression, and functional properties of a uniquely genetically labeled tendon cell subset in vivo. Using these approaches, we will test the hypothesis that this specifically labeled subset of tendon cells are resident tendon progenitors and that a specific pathway is required for proper tendon healing responses. Knowledge of this distinct cell population will impact our fundamental understanding of the diversity of cell types within the tendon and would significantly advance our ability to directly isolate and genetically manipulate these cells. This work is a crucial step towards studying unique tendon progenitor cell populations in their native environment and will provide the foundation for future studies aimed at elucidating mechanisms regulating their activities.