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

果蝇睾丸的适当功能和精子的一致产生需要独家 两个居民干细胞种群之间的协调 - 种系干细胞（GSC）和 体细胞干细胞。生殖细胞分化要求每个GSC女儿（a Gonialblast或GB）由囊肿的两个女儿包裹或包裹 干细胞谱系。睾丸细分市场坐在这两个中的子细胞的产生 干细胞群体通过对GSC施加细胞动力学延迟并需要细胞接触来进行干细胞群体 借助脱落的细胞，要触发细胞因子的最后一步。 有趣的是，细胞动力学停顿的长度有显着差异（30％至75％ 细胞周期）。为了使系统通过始终形成的三单元单元实现鲁棒性， 暂停长度的可变性表明，暂停，百科和触发器必须能够 每次补偿其他步骤的时间变化。这个预测很大的交叉 在两个干细胞谱系之间进行对话，以监测增殖率，干细胞数量和 细胞因子时机。先前的研究显示，在增殖中的协调程度很小 利基。实际上，我们的分析显示 GSC及其侧翼CYSC，没有证据表明CYSC在同一GSC的侧面是 狡猾地协调。这是我们假设它不是有丝分裂的，而是修饰的GSC细胞因子 结合串扰和监测两个干细胞之间的子细胞数量 人群生成了一个强大的系统来协调利基市场的子细胞释放。 我们的反馈模型预测，细胞因子时机缺陷将影响增殖 增殖或干细胞数的变化会影响细胞因子的时间。在这里，我们会的 通过 同时对两个干细胞群体进行成像。然后，我们将确定共同的程度 调节和交叉谈话在两个干细胞谱系之间以识别基础 确保结局的机制