Longitudinal imaging of stem cell coordination and cross-regulation in the testis niche

睾丸微环境中干细胞协调和交叉调节的纵向成像

• 批准号: 10336198
• 负责人: Kari Lenhart
• 金额: $ 5.75万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10336198
• 关键词: Affect; Biological Models; Cell Count; Cell Cycle; Cell Differentiation process; Cell Lineage; Cell physiology; Cells; Cyst; Cytokinesis; Daughter; Defect; Disease; Drosophila genus; Ensure; Environment; Excision; Feedback; Germ Cells; Goals; Image; Length; Mitotic; Molecular; Monitor; Outcome; Process; Production; Regulation; System; Testis; cell type; daughter cell; genetic manipulation; germline stem cells; insight; predictive modeling; serial imaging; sperm cell; stem cell biology; stem cell population; stem cells; tissue degeneration; tumorigenesis

Proper function of the Drosophila testis and consistent production of sperm requires exquisite coordination between two resident stem cell populations—the germline stem cells (GSCs) and the somatic Cyst Stem Cells. Germ cell differentiation requires that every one GSC daughter (a gonialblast, or Gb) is completed encased or encysted by precisely two daughters of the Cyst Stem Cell lineage. The testis niche coordinates production of daughter cells from these two stem cell populations by imposing a cytokinetic delay on the GSCs and requiring cell contact with encysting cells in order for abscission, the final step of cytokinesis, to be triggered. Interestingly, there is significant variability in the length of the cytokinetic pause (30 to 75% of the cell cycle). For the system to achieve robustness with a three-cell unit consistently formed, the variability in pause length suggests that the pause, encystment and trigger must be capable of each compensating for changes in timing of the other steps. This predicts substantial cross- talk between the two stem cell lineages to monitor proliferation rates, stem cell numbers and cytokinesis timing. Prior studies revealed only a small degree of coordination in proliferation in the niche. In fact, our analysis showed a lack of any significant mitotic synchrony between GSCs and their flanking CySCs and no evidence that CySCs flanking the same GSC were mitotically coordinated. Thus, we hypothesize that it is not mitosis, but modified GSC cytokinesis combined with cross-talk and monitoring of daughter cell numbers between the two stem cell populations, that generates a robust system to coordinate daughter cell release from the niche. Our feedback model predicts that defects in cytokinesis timing would affect proliferation while changes in proliferation or stem cell number would affect cytokinesis timing. Here, we will directly assess the degree of coordination between Gb encystment and abscission by simultaneous imaging of both stem cell populations. We will then determine the degree of co- regulation and cross talk between the two stem cell lineages to identify the underlying mechanisms that ensure a robust outcome

果蝇睾丸的正常功能和持续的精子生产需要精细