Apoptosis,or programmed cell death,is a complex,genetically-determined process involved in the development and maintenance of homeostasis in multicellular organisms.Dysregulation of apoptosis has been implicated in a number of diseases,including cancer and autoimmune disease.Thus,the investigation of apoptotic regulation has evoked considerable interest.Many apoptotic proteins have been shown to be post-translationally modulated,such as by protein cleavage,translocation,protein-protein interaction,and various post-translational modifications,which fall precisely within the range of proteomic analysis.Recently,contemporary proteomic technologies have achieved significant advances and have accelerated research in functional and chemical proteomics,which have been applied to the field of apoptosis research and have the potential to be a driving force for the field.This review highlights some of the major achievements in the application of proteomics in apoptosis research and discusses new directions and challenges for the near future.
WANG LiShun & CHEN GuoQiang Department of Pathophysiology,Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education of China
The discovery of induced pluripotent stem cells (iPSCs) is a promising advancement in the field of regenerative medicine. Previous studies have indicated that the teratoma-forming propensity of iPSCs is variable; however, the relationship between tumorigenic potential and genomic instability in human iPSCs (HiPSCs) remains to be fully elucidated. Here, we evaluated the malignant potential of HiPSCs by using both colony formation assays and tumorigenicity tests. We demonstrated that HiPSCs formed tumorigenic colonies when grown in cancer cell culture medium and produced malignancies in immunodeficient mice. Furthermore, we analyzed genomic instability in HiPSCs using whole-genome copy number variation analysis and determined that the extent of genomic instability was related with both the cells′ propensity to form colonies and their potential for tumorigenesis. These findings indicate a risk for potential malignancy of HiPSCs derived from genomic instability and suggest that quality control tests, including comprehensive tumorigenicity assays and genomic integrity validation, should be rigorously executed before the clinical application of HiPSCs. In addition, HiPSCs should be generated through the use of combined factors or other approaches that decrease the likelihood of genomic instability.
Yi LiangHui ZhangQi-Sheng FengMan-Bo CaiWen DengDajiang QinJing-Ping YunGeorge Sai Wah TsaoTiebang KangMiguel Angel EstebanDuanqing PeiYi-Xin Zeng