Identification of proteins related to epigenetic regulation in the malignant transformation of aberrant karyotypic human embryonic stem cells by quantitative proteomics.
Previous reports have demonstrated that human embryonic stem cells (hESCs) tend to develop genomic alterations and progress to a malignant state during long-term in vitro culture. This raises concerns of the clinical safety in using cultured hESCs. However, transformed hESCs might serve as an excellent model to determine the process of embryonic stem cell transition. In this study, ITRAQ-based tandem mass spectrometry was used to quantify normal and aberrant karyotypic hESCs proteins from simple to more complex karyotypic abnormalities. We identified and quantified 2583 proteins, and found that the expression levels of 316 proteins that represented at least 23 functional molecular groups were significantly different in both normal and abnormal hESCs. Dysregulated protein expression in epigenetic regulation was further verified in six pairs of hESC lines in early and late passage. In summary, this study is the first large-scale quantitative proteomic analysis of the malignant transformation of aberrant karyotypic hESCs. The data generated should serve as a useful reference of stem cell-derived tumor progression. Increased expression of both HDAC2 and CTNNB1 are detected as early as the pre-neoplastic stage, and might serve as prognostic markers in the malignant transformation of hESCs.
Institute of Reproductive and Stem Cell Engineering, Central South University, Changsha, China ; National Engineering and Research Center of Human Stem Cells, Changsha, China ; Key Laboratory of Stem Cells and Reproductive Engineering, Ministry of Health, Changsha, China.
Yi
Y
Sun
Key Laboratory of Molecular Biology for Infectious Diseases of Ministry of Education of China, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Yixuan
Y
Yang
Institute of Reproductive and Stem Cell Engineering, Central South University, Changsha, China.
Sicong
S
Zeng
Institute of Reproductive and Stem Cell Engineering, Central South University, Changsha, China ; National Engineering and Research Center of Human Stem Cells, Changsha, China ; Key Laboratory of Stem Cells and Reproductive Engineering, Ministry of Health, Changsha, China.
Yueqiu
Y
Tan
Institute of Reproductive and Stem Cell Engineering, Central South University, Changsha, China ; National Engineering and Research Center of Human Stem Cells, Changsha, China.
Guangxiu
G
Lu
Institute of Reproductive and Stem Cell Engineering, Central South University, Changsha, China ; National Engineering and Research Center of Human Stem Cells, Changsha, China ; Key Laboratory of Stem Cells and Reproductive Engineering, Ministry of Health, Changsha, China.
Ge
G
Lin
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology*; D016000:Cluster Analysis; D056915:DNA Copy Number Variations / Q000235:genetics; D053595:Embryonic Stem Cells / Q000378:metabolism*; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D006801:Humans; D007553:Isotope Labeling; D007621:Karyotyping; D013058:Mass Spectrometry; D051379:Mice; D058977:Molecular Sequence Annotation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism; D040901:Proteomics; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D059467:Transcriptome / Q000235:genetics
D009363:Neoplasm Proteins; D020543:Proteome