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.

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