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 许多成体组织通过干细胞的活性来替代因正常磨损而损失的细胞 细胞，但当损伤发生时可以使用完全不同的策略。理解和能力 控制再生，或因损伤而失去的组织或器官的再生，是一个长期的过程 生物学的长期目标。具有采用其他细胞的生物学特性的能力的细胞 特定条件下的类型或细胞可塑性是再生的关键因素。干 细胞甚至分化细胞都可以具有令人惊讶的可塑性，使它们能够 接受新的命运并重建受损的组织。这是为了响应改变而发生的 损伤时产生的微环境，但调节可塑性的机制很差 明白了。我们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生态位。优点包括相对简单 该组织和无与伦比的遗传工具集合来探测它的功能。之前， 我们发现，破坏果蝇睾丸会使正在分化的生殖细胞恢复到 生殖干细胞修复组织。我们最近发现静止的体细胞生态位细胞 受损后可转分化为新的成体干细胞。这里我们结合直播 成像、谱系追踪和单细胞转录组分析以确定现在的利基意义 损伤，然后激活程序来再生缺失的干细胞。我们还将揭开 正常组织中睾丸生态位中丰富的遗传途径的总体复杂性 周转，跟踪将信息从干细胞传递到其利基的候选信号。 我们的协同方法将增强对基本细胞和 驱动睾丸稳态和再生的分子机制，具有重要意义 对理解生育、再生和癌症的影响。