The role of Bmi1 in regulation of dental stem cells

描述（由申请人提供）：牙齿生物工程是非常感兴趣的，因为蛀牙和牙齿脱落构成了一个重要的公共卫生问题。此外，牙齿异常在许多颅面综合征中很常见，口腔的易接近性使牙齿成为器官置换的绝佳测试案例。彻底了解驱动牙齿更新和再生的分子过程对于努力建立新牙齿至关重要。我们正在使用小鼠切牙作为模型来理解干细胞促进牙齿组织更新的能力的机制，因为它由于成体干细胞的存在而不断生长。在这个应用程序中，我们建议学习的作用，转录控制的干细胞驱动的牙齿更新在小鼠切牙的重点是如何Bmi1调节这一过程。Bmi1是一种多梳组（Polycomb Group，PcG）蛋白，是多种组织中干细胞自我更新所必需的。该申请中提出的实验将首先使用遗传谱系追踪方法来确定切牙中哪些分化的细胞类型来自表达Bmi 1的干细胞。接下来，我们将探索Bmi1在体内和体外切牙干细胞自我更新和分化中的功能作用。最后，我们将确定Bmi1的遗传靶点，并确定它们在牙齿干细胞中的功能。这些研究将促进我们对自然界如何在牙齿再生中使用干细胞的理解。这些信息将为未来基于干细胞的牙齿生物工程提供信息。

DESCRIPTION (provided by applicant): Tooth bioengineering is of great interest, because dental decay and tooth loss constitute an important public health issue. Additionally, tooth anomalies are common in many craniofacial syndromes, and the easy accessibility of the oral cavity makes teeth an excellent test case for organ replacement. A thorough understanding of the molecular processes that drive tooth renewal and regeneration will be crucial to efforts to build new teeth. We are using the mouse incisor as a model for understanding the mechanisms that underlie the ability of stem cells to contribute to renewal of dental tissues, because it grows continuously due to the presence of adult stem cells. In this application, we propose to learn about the role of transcriptional control of stem cell-driven tooth renewal in the mouse incisor by focusing on how Bmi1 regulates this process. Bmi1 is a Polycomb Group (PcG) protein that is required for stem cell self-renewal in multiple tissues. The experiments proposed in the application will first identify which differentiated cell types in the incisor arise from Bmi1- expressing stem cells using genetic lineage tracing approaches. Next, we will explore the functional role of Bmi1 in incisor stem cell self-renewal and differentiation in vivo and in vitro. Finally, we will identify genetic targets of Bmi1 and determine their function in dental stem cells. These studies will advance our understanding of how nature normally uses stem cells in dental regeneration. Such information will inform future efforts aimed at stem cell-based tooth bioengineering.