Stem Cell and Leukaemia Proteomics Laboratory, School of Cancer and Enabling Sciences, Manchester Academic Health Science Centre, The University of Manchester, Christie's NHS Foundation Trust, Wolfson Molecular Imaging Centre, Withington, Manchester, UK.
J Cell Physiol. 2011 Oct;226(10):2478-83. doi: 10.1002/jcp.22610.
Stem cells are defined by their ability to self-renew and to differentiate, the processes whereby these events are achieved is the subject of much investigation. These studies include cancer stem cell populations, where eradication of this specific population is the ultimate goal of treatment. Whilst cellular signalling events and transcription factor complex-mediated changes in gene expression have been analysed in some detail within stem cells, full systematic understanding of the events promoting self-renewal or the commitment process leading to formation of a specific cell type require a systems biology approach. This in turn demands a need for proteomic analysis of post-translational regulation of protein levels, protein interactions, protein post-translational modification (e.g. ubiquitination, methylation, acetylation, phosphorylation) to identify networks for stem cell regulation. Furthermore, the phenomenon of induced pluripotency via cellular reprogramming also can be understood optimally using combined molecular biology and proteomics approaches; here we describe current research employing proteomics and mass spectrometry to dissect stem cell regulatory mechanisms.
干细胞的定义特征为自我更新和分化的能力,这些事件的发生过程是许多研究的主题。这些研究包括癌症干细胞群体,其中消除这种特定群体是治疗的最终目标。虽然在干细胞中已经详细分析了细胞信号事件和转录因子复合物介导的基因表达变化,但要全面系统地了解促进自我更新或导致特定细胞类型形成的事件,需要系统生物学方法。这反过来又需要对蛋白质水平的翻译后调控、蛋白质相互作用、蛋白质翻译后修饰(如泛素化、甲基化、乙酰化、磷酸化)进行蛋白质组学分析,以鉴定干细胞调控网络。此外,通过细胞重编程诱导的多能性现象也可以通过结合分子生物学和蛋白质组学方法来最佳地理解;在这里,我们描述了当前使用蛋白质组学和质谱法来剖析干细胞调控机制的研究。