Mechanisms of specification, quiescence, and regeneration of primordial germ cells

原始生殖细胞的规范、静止和再生机制

• 批准号: 10472183
• 负责人: GARY M WESSEL
• 金额: $ 4.15万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10472183
• 关键词: Administrative Supplement; Biological Sciences; Biomedical Research; Cells; Chromatin; Communities; Development; Doctor of Philosophy; Embryo; Ensure; Environment; Event; Fellowship; Genetic Transcription; Germ Cells; Germ Lines; Goals; Human; In Vitro; International; Journals; Light; Mission; Modeling; Molecular; Mus; Natural regeneration; Nodal; PRDM1 gene; Parents; Pathway interactions; Persons; Publishing; Qualifying; Regulation; Research; Research Training; Resolution; Signal Induction; Signal Pathway; Signal Transduction; Starfish; Structure of primordial sex cell; Testing; Training; Work; cell type; experimental study; in vivo; meetings; optogenetics; parent grant; receptor; response; single cell mRNA sequencing; transcriptome; translational applications; virtual

Summary Increasing the diversity in our BioMedical research workforce is key to maximize progress in our understanding of the basic and translational applications of life sciences. The thesis project of Gerardo Reyes will extend the research depth and breadth for understanding germ line formation by inductive interactions using the sea star. Mr. Reyes’ passed his qualifying examination and defense of his thesis proposal in May 2021. His proposal builds upon the Parent Research Plan #2 (summarized here): Targets and mechanisms of inductive signaling for specification of the primordial germ cells (PGCs). Significant progress has been made in research on mouse and human iPScells induced to form PGCs in vitro. We focus our work instead on in vivo analysis of PGC specification during intercellular signaling mechanisms and directly observe rapid acquisition of induced cell fates in live embryos. This Administrative Supplement will contribute by 1) Determining the hierarchy of signaling pathways and developmental timing required for inductive germline specification. 2) Identifying the molecular mechanism for commitment to the germline by induction mechanisms in vivo. We hypothesize that once germ cells are formed, they rapidly insulate themselves from local embryonic signaling mechanisms and instead transition to a committed cell type with a unique transcriptome, chromatin landscape, and signal response profile. We will test this model by single cell mRNA sequencing and optogenetic control over signaling (light-inducible Nodal receptor) and transcriptional events at a single cell resolution. The thesis research of Gerardo Reyes focuses on identifying the inductive pathway for BLIMP1 expression and to identify the BLIMP1 targets of regulation in the germ line. The research of Mr. Reyes will be instrumental to the core principles of the parent grant and to the mission of diversifying the research workforce by direct training of historically underrepresented candidates.

总结 增加我们生物医学研究队伍的多样性是最大限度地提高我们的进展的关键。 了解生命科学的基础和转化应用。毕业设计 Gerardo Reyes将扩展研究深度和广度，以了解生殖系 通过使用海星星星的诱导相互作用形成。雷耶斯先生通过了资格考试 于2021年5月完成论文答辩。他的建议建立在 父母研究计划#2（总结在这里）：诱导信号的目标和机制 原始生殖细胞（PGCs）的规格。取得重大进展 在体外诱导小鼠和人iPS细胞形成PGCs的研究。我们的工作重点 相反，在细胞间信号传导机制期间PGC特化的体内分析， 直接观察活胚胎中诱导细胞命运的快速获得。这一行政 补充剂将通过以下方式做出贡献：1）确定信号传导途径的层次结构， 诱导生殖系规格所需的发育时间。2)识别 通过体内诱导机制向生殖系定型的分子机制。 我们假设，一旦生殖细胞形成，它们迅速将自己与局部免疫系统隔离开来， 胚胎信号传导机制，而不是过渡到一个独特的承诺细胞类型， 转录组、染色质景观和信号响应谱。我们将通过以下方式测试此模型： 单细胞mRNA测序和信号传导的光遗传学控制（光诱导Nodal 受体）和转录事件。Gerardo的论文研究 Reyes专注于确定BLIMP1表达的诱导途径，并确定BLIMP1表达的诱导途径。 BLIMP1在生殖细胞系中的调节靶点。雷耶斯先生的研究将有助于 家长补助金的核心原则和多样化的研究队伍的使命 通过直接培训历史上代表性不足的候选人。