Defining mechanisms driving salivary gland regeneration

项目摘要/摘要 基于干细胞的治疗疾病和恢复器官功能的疗法的发展导致了一个关键的 需要鉴定颅面组织中的内源性干细胞及其调节因子。我们已经取得了重大进展 破译头面部器官系统唾液腺中干细胞的身份和调节 深受慢性疾病(如衰老、自身免疫、癌症)的影响，而这些疾病几乎没有症状 没有长期的恢复性治疗。然而，尽管在这一领域取得了进展，我们仍然非常 在了解驱动器官修复和再生的机制的早期阶段。因此，基于我们的 先前的研究揭示了唾液祖细胞的身份和功能以及胆碱能神经的新作用 在形态发生和更新计划中，我们试图阐明驱动唾液腺再生的机制。 通过探索4个重要问题：(1)唾液干细胞如何使器官更新？(2)神经如何 控制器官动态平衡和再生？(3)衰老对唾液干细胞有何影响？最后，(4) 唾液腺结构是如何形成的？我们将结合以下几个方面回答这些问题 在小鼠和人类组织中的发育和再生方法，以及一群分子， 生化、成像和细胞生物学检测。这里的结果将揭示新的细胞和分子 以干细胞为基础的治疗方法的发展所需的机制逆转这些和 其他器官系统。

Project Summary/Abstract The development of stem cell-based therapies for curing disease and restoring organ function has led to a critical need to identify endogenous stem cells and their regulators in craniofacial tissues. We have made significant inroads into deciphering stem cell identity and regulation in the salivary gland, a craniofacial organ system profoundly affected by chronic diseases (e.g., aging, autoimmunity, cancer) for which there are few symptomatic treatments and no long-term restorative therapies. However, despite progress in the field, we are still very much in the early stages of understanding the mechanisms driving organ repair and regeneration. Thus, based our previous studies revealing the identity and function of salivary progenitors and novel roles of cholinergic nerves in morphogenic and renewal programs, we seek to elucidate the mechanisms driving salivary gland regeneration by exploring 4 significant questions: (1) How do salivary stem cells enable organ renewal? (2) How do nerves control organ homeostasis and regeneration? (3) How does aging impact salivary stem cells? And finally, (4) How is salivary gland architecture created? We will answer these questions using a combination of developmental and regenerative approaches in mice and human tissue together with a bevy of molecular, biochemical, imaging and cell biological assays. Outcomes here will uncover novel cellular and molecular mechanisms required for the development of stem cell based therapeutics for reversing damage in these and other organ systems.