The BCL-2 family controls stem cell identity by regulating mitochondrial dynamics and priming

BCL-2 家族通过调节线粒体动力学和启动来控制干细胞身份

• 批准号: 10456226
• 负责人: Vivian Gama
• 金额: $ 39.18万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10456226
• 关键词: Address; Apoptosis; BCL-2 Protein; BCL2 gene; Biochemistry; Cell Nucleus; Cells; Cellular biology; Event; Family; Family member; Genetic; Mediating; Mitochondria; Molecular; Molecular Biology; Protein Family; Regulation; Research; Role; Signal Transduction; Translating; interdisciplinary approach; novel; stem cell biology; stem cells; transcription factor

Summary Research in the stem cell field has traditionally focused on understanding key transcriptional factors that provide pluripotent cell identity. However, much less is known about other critical non-transcriptional signaling networks that govern stem cell identity and lineage commitment. Our preliminary studies suggest an emerging landscape in which the BCL-2 family of proteins has an active role in maintaining cell identity independently of its role in mitochondrial outer permeabilization. We will employ a multidisciplinary approach combining molecular biology, biochemistry, genetics, and cell biology to address fundamental questions such as: What are the signaling events involved in the role of BCL-2 family maintaining a fragmented mitochondrial network in stem cells independently of its role in apoptosis? Are mitochondrial dynamics mediated through the BCL-2 family a requirement for cellular reprogramming? What are the signaling mechanisms involved in translating the information from the mitochondria into the nucleus to ultimately modulate cell fate? We plan to combine our expertise in mitochondrial and stem cell biology with state-of- the-art approaches to seek answers to these questions and reveal novel functions of the BCL-2 family in stem cell identity and commitment.

概括 传统上，干细胞领域的研究集中在理解关键转录因素上 提供多能细胞身份。但是，关于其他关键非转录的知之甚少 控制干细胞身份和谱系承诺的信号网络。我们的初步研究表明 Bcl-2蛋白质家族在维持细胞身份中具有积极作用的新兴景观 它独立于其在线粒体外透化中的作用。我们将采用多学科的方法 结合分子生物学，生物化学，遗传学和细胞生物学来解决基本问题 例如：Bcl-2家族的作用中涉及哪些信号事件，保持了碎片 干细胞中的线粒体网络与其在凋亡中的作用无关？是线粒体动力学 通过Bcl-2家族介导的细胞重编程要求？信号是什么 将信息从线粒体转化为核的机制最终 调节细胞命运？我们计划将线粒体和干细胞生物学方面的专业知识与最新 Art方法寻求这些问题的答案并揭示Bcl-2家族的新功能 干细胞的身份和承诺。