Regulation of cellular plasticity and regeneration in Drosophila spermatogenesis

摘要 许多成人组织通过干细胞的活动来修复因正常磨损而丢失的细胞。 细胞，但当伤害发生时，可以使用完全不同的策略。理解和理解 控制再生，即损伤后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。具有吸收其他细胞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。茎 细胞，甚至分化后的细胞，都具有惊人的可塑性，使它们能够 接受新的命运，重建受损的组织。这发生在对改变的反应中 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 干细胞和它们的微环境，或利基。优点包括相对简单 以及无与伦比的基因工具来探测它的功能。此前， 我们发现，破坏果蝇睾丸会转化为分化生殖细胞恢复到 生殖系干细胞来修复组织。我们最近发现静止的体细胞壁龛细胞 受损后可以转分化为新的体细胞干细胞。在这里我们结合了现场直播 成像、谱系追踪和单细胞转录图谱以确定现在的利基感觉 损伤，然后激活程序(S)以再生丢失的干细胞。我们还将揭开 正常组织中睾丸壁龛丰富的遗传途径的整体复杂性 更替，跟进候选人信号，将信息从干细胞传递到它们的利基。 我们的协同方法将增强对基本细胞和 睾丸内动态平衡和再生的分子机制，这具有重要的意义 对理解生育、再生和癌症的影响。

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.