Regulation of cellular plasticity and regeneration in Drosophila spermatogenesis

果蝇精子发生中细胞可塑性和再生的调节

• 批准号: 10160926
• 负责人: Erika L Matunis
• 金额: $ 40.94万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10160926
• 关键词: Adopted; Adult; Automobile Driving; Biological; Biological Models; Biology; Cell Differentiation process; Cells; Collection; Drosophila genus; Fertility; Genetic; Germ Cells; Goals; Homeostasis; Image; Injury; Malignant Neoplasms; Molecular; Natural regeneration; Normal tissue morphology; Organ; Pathway interactions; Property; Signal Transduction; Spermatogenesis; Testis; Therapeutic; Tissues; Work; cell growth regulation; cell type; genome-wide; germline stem cells; interest; mature animal; programs; response; response to injury; stem cell biology; stem cells; tissue regeneration; tissue repair; tool; transcriptomics

Abstract Many adult tissues replace cells lost due to normal wear and tear through the activity of stem cells, but can use entirely different strategies when injury occurs. The ability to understand and control regeneration, or the regrowth of lost tissues or organs in response to injury, is a long- standing goal in biology. Cells with the capacity to adopt the biological properties of other cell types under specific conditions, or cellular plasticity, are key contributors to regeneration. Stem cells and even differentiated cells can have surprising degrees of plasticity, allowing them to adopt new fates and rebuild damaged tissues. This happens in response to altered microenvironments that arise upon injury, but the mechanisms that regulate plasticity are poorly understood. We have developed the Drosophila testis as a model system to study the biology of stem cells and their microenvironments, or niches. Advantages include the relative simplicity of this tissue and an unparalleled collection of genetic tools to probe it functionally. Previously, we showed that damaging the Drosophila testis converts differentiating germ cells to revert to germline stem cells to repair the tissue. We recently found that quiescent somatic niche cells can transdifferentiate into new somatic stem cells upon damage. Here we combine live imaging, lineage tracing and single cell transcriptomic profiling to determine now niches sense damage and then activate program(s) to regenerate missing stem cells. We will also uncover the overall complexity of the genetic pathways enriched in the testis niche during normal tissue turnover, following up on candidate signals that relay information from stem cells to their niche. Our synergistic approach will enhance the understanding of the fundamental cellular and molecular mechanisms driving homeostasis and regeneration in the testis, which has important implications for understanding fertility, regeneration and cancer.

抽象的 许多成年组织取代因茎活动正常磨损而导致的细胞损失 细胞，但是当受伤时可以使用完全不同的策略。理解和 对照再生或损失的组织或器官响应损伤的再生是长期的 生物学的常规目标。具有采用其他细胞生物学特性的能力的细胞 在特定条件下或细胞可塑性下的类型是再生的关键因素。干 细胞甚至分化的细胞可能具有令人惊讶的可塑性，从而使它们能够 采用新的命运并重建受损的组织。这是为了改变变化而发生 受伤后出现的微环境，但是调节可塑性的机制很差 理解。我们已经开发了果蝇睾丸作为研究生物学的模型系统 干细胞及其微环境或利基。优点包括相对简单性 该组织和无与伦比的遗传工具集合以探测其功能。之前， 我们表明，损害果蝇睾丸会转换分化的生殖细胞以恢复为 种系干细胞修复组织。我们最近发现静态的体细胞细胞 损伤后可以转变为新的体积干细胞。在这里我们结合现场 成像，谱系跟踪和单细胞转录组分析，以确定壁nighes Sense 损坏然后激活程序以再生缺失的干细胞。我们也会发现 正常组织中富集在睾丸小境中的遗传途径的总体复杂性 营业额，跟进候选信号，这些信号将信息从干细胞转移到其利基市场。 我们的协同方法将增强对基本细胞的理解和 睾丸中驱动体内平衡和再生的分子机制，这具有重要 了解生育能力，再生和癌症的意义。