Entosis作为一种新的上皮细胞分裂监测机制的概念性验证

细胞分裂是最基本的生物学过程，及时清除异常的子代细胞对于维持组织和遗传稳态至关重要，该机制的异常往往导致疾病发生。Entosis可以通过Cell-in-cell结构导致内部细胞死亡，被认为是第四类细胞死亡方式，但是其生物学意义并不清楚。前期研究中，我们发现cell-in-cell结构形成与上皮细胞分裂紧密偶联，可以选择性的内化并清除一部分子代细胞，提示该机制可能作为一种细胞分裂监测（mitotic surveillance）的全新机制。本研究拟基于已建立的成熟entosis模型，借助高通量显微成像技术追踪分析细胞分裂和cell-in-cell结构形成的动态偶联过程，揭示子代细胞清除的选择性开关，结合临床标本基因表达谱分析，利用遗传学和细胞生物学手段解析调控两种过程偶联的分子和细胞学机制，在细胞和动物水平完成概念性验证，为进一步揭示该机制在维持机体组织和遗传稳态中的作用奠定基础。

Cell division is a fundmental biological process that requires in-time elimination of abnormal daughter cells to maintain tissue and genetic homeostasis, dysregulation of which is tightly associated with diseases. Entosis is a process that generally lead to the death of internalized cells via cell-in-cell structures, therefore regarded as type IV cell death, however with biological functions unknown yet. In our previous study, we found formation of cell-in-cell structures was tightly coupled with mitotic cell division, which led to selective internalization and subsequent death of a portion of mitotic daughter cells. Therefore, we hypothesize that entosis may serve as a novel mechanism of mitotic surveillance. In this study, based on the established entosis model and by taking advantage of high throughput time lapse imaging, we attempt to explore the key switch controlling selective elimination of mitotic daughter cells via track the dynamic processes coupling cell division and cell-in-cell formation, and together with expression profiling of patient cancer tissues to genetically dissect their molecular and cellular mechanisms. We hope to complete the proof of concept for our hypothesis in both cell cultures in vitro and animal tissues in vivo in this study, and setting basis for subsequently uncovering the biological roles of cell-in-cell structures in maintaining tissue homeostasis and genetic integrity.