EAGER: Cell Excretion, a Novel Mechanism of Cell Clearance

在许多动物组织中，基因程序化的细胞死亡形式在整个生命过程中以很高的速率发生，因此需要快速清除产生的细胞尸体以保持组织稳态。在典型细胞清除机制中，凋亡细胞的残余物被吞噬细胞吞噬并在溶酶体中降解。然而，最近的研究表明，其他形式的细胞清除对动物的发育和生理也很重要。这一建议的目的是表征一个这样的新过程在涡虫扁虫地中海Schmidtea。拟议的实验将解决光暴露引发色素细胞死亡的假设，但由此产生的尸体被重新分配到肠道并排出体外，而不是被溶酶体降解。学生研究人员将获得当前技术的宝贵经验，包括RNA干扰和共聚焦显微镜，发展技能，为他们的科学事业和/或生物科学研究生课程做好准备。因此，与该奖项相关的工作将加强新罕布什尔州扩大未来STEM专业人才储备的努力，这是该州EPSCoR计划的核心目标。PI提供的初步数据表明，长时间暴露在强烈的可见光下会导致成年涡虫身体完全脱色，这与从肠道排出大量重色素物质有关。通过揭示这种反应背后的细胞机制，该项目的研究部分可能为自我更新的成年组织如何清除死亡或受损细胞提供新的见解。组织学分析将结合双重标记方法，结合TUNEL和荧光原位杂交（FISH），以表征光诱导的色素脱色反应的细胞机制，这种反应似乎是由色素细胞的选择性消除引起的。该研究项目将通过补充我们对典型凋亡细胞清除途径的现有知识，显著推进我们对后生动物组织稳态的理解。这项研究的结果将通过科学会议报告和在同行评议的期刊上发表来传播。

Genetically programmed forms of cell death occur at a high rate throughout life in many animal tissues, necessitating rapid clearance of the resulting cell corpses to preserve tissue homeostasis. In the canonical cell clearance mechanism, remnants of apoptotic cells are engulfed by phagocytic cells and degraded in the lysosome. However, recent work has revealed that alternative forms of cell clearance are also important for meatazoan development and physiology. The objective of this proposal is to characterize one such novel process in the planarian flatworm Schmidtea mediterranea. The proposed experiments will address the hypothesis that light exposure triggers pigment cell death, but that the resulting corpses are redistributed to the gut and excreted, instead of being subjected to lysosomal degradation. Student researchers will gain valuable experience in current techniques, including RNA interference and confocal microscopy, developing skills that prepare them for scientific careers and/or graduate programs in the biological sciences. The work associated with this award will therefore augment the state of New Hampshire's efforts to expand the pipeline for future STEM professionals, a central goal of the state EPSCoR program.Preliminary data produced by the PI show that prolonged exposure to intense visible light induces complete bodily depigmentation in adult planarians and that this is associated with excretion of large amounts of heavily pigmented material from the gut. By revealing the cellular mechanisms underlying this response, the research component of this project is likely to provide new insight into how self-renewing adult tissues clear dead or damaged cells. Histologic analyses will be combined with a double-labeling approach incorporating TUNEL and fluorescent in situ hybridization (FISH) to characterize the cellular mechanisms of a light-induced depigmentation response that appears to result from selective elimination of pigment cells. The research project will significantly advance our understanding of metazoan tissue homeostasis by complementing our existing knowledge of the canonical apoptotic cell clearance pathway. Results from the study will be disseminated through scientific conference presentations and by publication in peer-reviewed journals.