Sheng Yang and Ge Lin contributed equally to this work.
Tumor progression of culture-adapted human embryonic stem cells during long-term culture
Article first published online: 9 MAY 2008
Copyright © 2008 Wiley-Liss, Inc.
Genes, Chromosomes and Cancer
Volume 47, Issue 8, pages 665–679, August 2008
How to Cite
Yang, S., Lin, G., Tan, Y.-Q., Zhou, D., Deng, L.-Y., Cheng, D.-H., Luo, S.-W., Liu, T.-C., Zhou, X.-Y., Sun, Z., Xiang, Y., Chen, T.-J., Wen, J.-F. and Lu, G.-X. (2008), Tumor progression of culture-adapted human embryonic stem cells during long-term culture. Genes Chromosom. Cancer, 47: 665–679. doi: 10.1002/gcc.20574
- Issue published online: 3 JUN 2008
- Article first published online: 9 MAY 2008
- Manuscript Accepted: 14 APR 2008
- Manuscript Received: 20 SEP 2007
- The Hi-Tech Research And Development of China. Grant Number: 2006 AA02A102
- The National Basic Research Program of China. Grant Number: 973 program No. 00CB 51010
- Bureau Science and Technology Key Project Funds of Hunan Province. Grant Number: 03SSY2001
- Ministry of Education of China (Research Fund for the Doctoral Program). Grant Number: 20030533002
- The Key Project of Chinese Ministry of Education. Grant Number: 105131
Human embryonic stem cells (hESCs) during long-term culture acquire chromosomal changes similar to those occurring in tumorigenesis. This was raised concerns about the progression from hESCs to malignant cells. This study aimed to investigate the changes in chromosomes, cell phenotype, and genes in culture-adapted hESCs to ascertain whether tumorigenic transformation occurred. By cytogenetic analysis we found progressive karyotypic changes from simple to complex in chHES-3, one of the hESC lines established in our laboratory, during a long-term suboptimal culture. We further compared chHES-3 cells at different karyotypic stages in cell surface markers, in vivo differentiation, cell cycle, apoptosis, and gene expression profiles. We found that the karyotypically aberrant chHES-3 had higher S-phase fraction in cell cycle distributions and antiapoptosis ability. In vivo differentiation of karyotypically normal chHES-3 resulted in relatively mature teratoma, whereas karyotypically aberrant chHES-3 formed immature teratoma (grade III), in which more primary neural epithelium was revealed by pathological analysis. The microarray analysis and real-time PCR results showed that some oncogenes were upregulated in karyotypically aberrant chHES-3 cells, whereas the genes related to differentiation were downregulated, and that Wnt signal pathway was activated. In conclusion, chHES-3 cells underwent deregulation of self-renewal and dysfunction of related genes in long-term culture adaptation, leading to malignant transformation. © 2008 Wiley-Liss, Inc.