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: 10224684
• 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 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10224684
• 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.

摘要 干细胞领域的研究传统上侧重于了解关键的转录因子， 提供多能细胞身份。然而，对其他关键的非转录因子的了解要少得多。 管理干细胞身份和血统承诺的信号网络。我们的初步研究表明 Bcl2蛋白家族在维持细胞特性方面发挥积极作用的新格局 与其在线粒体外通透性中的作用无关。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 如：哪些信号事件参与了bcl2家族维持碎片化的作用 干细胞中的线粒体网络独立于其在细胞凋亡中的作用？线粒体动力学 通过bcl2家族的调节是细胞重新编程的需要吗？信号是什么？ 参与将信息从线粒体翻译到细胞核的机制，最终 来决定细胞的命运？我们计划将我们在线粒体和干细胞生物学方面的专业知识与 寻求这些问题的答案并揭示bcl-2家族在 干细胞的身份和承诺。