The role of Bmi1 in regulation of dental stem cells

描述（由申请人提供）：牙齿生物工程是一个非常有趣的研究，因为蛀牙和牙齿脱落是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试验案例。彻底了解驱动牙齿更新和再生的分子过程对于努力构建新牙齿至关重要。我们使用小鼠门牙作为模型，以了解干细胞促进牙组织更新能力的机制，因为它由于成体干细胞的存在而持续生长。在这项应用中，我们建议通过关注Bmi1如何调节这一过程来了解干细胞驱动的小鼠门牙更新的转录控制作用。Bmi1是多种组织中干细胞自我更新所必需的Polycomb Group （PcG）蛋白。应用程序中提出的实验将首先使用遗传谱系追踪方法确定门牙中哪些分化细胞类型来自表达Bmi1的干细胞。接下来，我们将探讨Bmi1在体内和体外门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的遗传靶点并确定其在牙干细胞中的功能。这些研究将促进我们对大自然如何在牙齿再生中正常使用干细胞的理解。这些信息将为未来以干细胞为基础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.