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.

概括 增加生物医学研究劳动力的多样性是最大程度地提高我们的进步的关键 了解生命科学的基本和翻译应用。论文项目 Gerardo Reyes将扩展研究深度和广度，以了解细菌线 使用海星通过感应相互作用形成。雷耶斯先生通过了他的资格 审查和辩护他的论文提议于2021年5月。他的提议建立在 家长研究计划＃2（在此处汇总）：归纳信号的目标和机制 用于原始生殖细胞（PGC）的规范。已经取得了重大进展 小鼠和人类IPSCELS的研究诱导在体外形成PGC。我们集中工作 相反，在细胞间信号传导机制中对PGC规范的体内分析和 直接观察到活体胚胎中诱导的细胞命运的快速获取。这个行政 补充将通过1）确定信号通路的层次结构和 归纳种系规范所需的发育时机。 2）确定 通过体内诱导机制对种系承诺的分子机制。 我们假设一旦形成生殖细胞，它们就会迅速与局部隔离 胚胎信号传导机制，而是过渡到具有独特的授权单元格 转录组，染色质景观和信号响应轮廓。我们将通过 单细胞mRNA测序和对信号传导的光遗传学控制（光诱导节点 受体）和单个细胞分辨率下的转录事件。 Gerardo的论文研究 雷耶斯专注于识别Blimp1表达的归纳途径，并确定 Blimp1在种系中调节的目标。雷耶斯先生的研究将有助于 父母赠款的核心原则和使研究人员多样化的使命 通过直接培训历史上代表性不足的候选人。