Inductive germ cell specification and self-assembly of sexually dimorphic gonads

性二态性性腺的诱导生殖细胞规范和自组装

• 批准号: 10702891
• 负责人: Erin Davies
• 金额: $ 26万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10702891
• 关键词: Adult; Amputation; Anatomy; Area; Atlases; Biological Markers; Biological Models; Candidate Disease Gene; Cells; Embryonic Development; Female; Future; Genetic; Germ Cells; Gonadal structure; Homeostasis; Imaging Techniques; Morphogenesis; Natural regeneration; Organ; Outcome; Platyhelminths; Process; Protocols documentation; Reaction; Regulation; Reproductive system; Resources; Signal Induction; Source; Starvation; Structure; Techniques; Time; Tissues; Transgenic Organisms; Ursidae Family; cell type; falls; germline stem cells; gonad development; imaging modality; male; nano; postnatal; programs; reproductive; screening; segregation; self assembly; self organization; sexual dimorphism; single-cell RNA sequencing; stem cell fate; stem cells; transcriptomics

Dr. Xintao Fan has made steady progress since the initiation of this project in Fall 2021, and has brought new techniques to bear in this emerging model system. He developed hybridization chain reaction protocols to visualize candidate aPSC and early germ cell biomarkers, including nanos and vasa homologs. He has characterized both postnatal and de novo gonad formation following amputation or starvation using cell type-specific markers on fixed tissue. He has identified conditions critical to the capture of biologically impactful time points for single cell RNA-Seq transcriptomic analysis as part of a collaborative atlas-building project to identify cellular constituents of the reproductive system, and candidate genes for future functional perturbation. A key area of focus in the upcoming fiscal year will be generating transgenic lines that allow us to visualize and track the dynamics of adult PSCs and the outcome of asymmetric divisions giving rise to germline stem cells. We will develop live imaging methods to observe gonad morphogenesis in different adult contexts, and will begin functional screening of candidate genes implicated in the establishment of germline stem cell fate(s).

自从2021年秋季开始该项目以来，Xintao Fan博士一直在稳步进步，并为这种新兴模型系统带来了新的技术。他开发了杂交链反应方案，以可视化候选APSC和早期生殖细胞生物标志物，包括纳米和VASA同源物。他的表征是在截肢后使用固定组织上细胞类型特异性标记的截肢后产后和从头性腺的形成。他确定了对捕获单细胞RNA-seq转录组分析的生物影响力时间点至关重要的条件，这是协作地图集建造项目的一部分，以鉴定生殖系统的细胞成分，以及用于未来功能扰动的候选基因。在即将到来的会计年度中，重点的关键领域将产生转基因线，使我们能够可视化和跟踪成年PSC的动力学以及不对称分裂的结果，从而导致种系干细胞。我们将开发实时成像方法，以观察不同成人背景下的性腺形态发生，并将开始对与种系干细胞命运建立有关的候选基因的功能筛查。