细胞命运和身份的维持和转变是多细胞生物的基础。肿瘤发生和体细胞重编程可以看做是细胞命运和身份发生异常改变的结果，但这些异常改变通常都是小概率事件，因为多数异常细胞都会因DNA损伤激活p53通路而出现凋亡或衰老。然而，细胞如何监测其身份及其异常变化却不清楚。脊椎动物细胞的纺锤体基质是本项目合作者郑诣先教授实验室发现的有丝分裂纺锤体中微管之外的基质成分，我们近年来的合作研究显示它不仅参与调节有丝分裂，还可能调节细胞的命运和身份。本申请拟以我们在前期合作研究中通过对小鼠胚胎干细胞进行RNAi筛选而发现的一个新的纺锤体基质蛋白质BuGZ为切入点，深入探讨纺锤体基质在细胞命运和身份的维持和调控中的功能，为纺锤体基质这一新的研究领域的发展做出重要贡献。同时，希望能够发现安全高效地进行体外体细胞重编程的新方法，并从独特的角度发现肿瘤治疗的新靶点。

Cell fate and its maintenance and conversion are the basis of multicellular organisms. Tumorigenesis and somatic reprogramming can be considered as consequences of abnormal changes of cell fate. Abnormal changes are usually events of small probability, since most abnormal cells eventually undergo apoptosis or aging because of DNA damage which activates p53 pathway. However, what is the underlying mechanism and how cells monitor their status and abnormal change are poorly understood. Dr. Yixian Zheng’s laboratory discovered that in addition to microtubules, spindle matrix exists in mitotic spindles of vertebrate cells. Our recent joint research revealed that the matrix is not only involved in mitotic regulation, but may also play a vital role in cell fate specification and maintenance. Through previous joint project granted by NSFC, we identified a new spindle matrix protein BuGZ after RNAi screen in embryonic stem cells. In this project we intend to further investigate how BuGZ regulates cell fate, thus exploring the novel function of spindle matrix protein(s) in an uncharted territory of stem cell maintenance and function. Our research proposed herein may also lead to improved approaches to somatic reprogramming with high efficiency and biological safety and provide a new angle for cancer drug target discovery.