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

摘要 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 了解生命科学的基本应用和翻译应用。的毕业论文项目 杰拉尔多·雷耶斯将扩展研究深度和广度，以了解生殖系 利用海星感应相互作用形成的。雷耶斯先生通过了资格赛 2021年5月对他的论文提案进行审查和辩护。他的建议建立在 父母研究计划2(在此总结)：诱导信号的目标和机制 关于原始生殖细胞(PGC)的规范。在以下方面取得了重大进展 体外诱导小鼠和人IPS细胞形成PGCs的研究。我们专注于我们的工作 取而代之的是对细胞间信号机制和PGC规范的体内分析 直接观察活体胚胎中诱导细胞命运的快速获得。此管理 补充将有助于1)确定信号通路的层次结构和 诱导生殖系规格所需的发育时序。2)识别 在体内通过诱导机制向生殖系承诺的分子机制。 我们假设，一旦生殖细胞形成，它们就会迅速将自己与局部隔绝 胚胎信号机制，而不是过渡到承诺的细胞类型 转录组，染色质景观，和信号响应图谱。我们将通过以下方式测试此模型 单细胞信使核糖核酸测序与光遗传信号调控(光诱导结节 受体)和转录事件在单个细胞分辨率。关于杰拉尔多的论文研究 雷耶斯专注于确定BLIMP1表达的诱导途径，并确定 BLIMP1是生殖系调控的靶标。雷耶斯先生的研究将有助于 母基金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。

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.