Related Experiment Videos
Genomic alterations in cultured human embryonic stem cells
Anirban Maitra1, Dan E Arking, Narayan Shivapurkar
1McKusick-Nathans Institute of Genetic Medicine, Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Nature Genetics
|September 6, 2005
Summary
Cultured human embryonic stem cell (hESC) lines accumulate genetic and epigenetic alterations during tissue culture. These genomic changes, similar to those in cancer, may impact hESC usability for therapeutic applications.
Area of Science:
- Stem cell biology
- Genomics
- Cancer biology
Background:
- Human embryonic stem cell (hESC) lines are crucial for research and therapy.
- Cellular division in hESCs can lead to spontaneous mutations.
Purpose of the Study:
- To assess the genomic integrity of hESC lines over time in tissue culture.
- To identify genetic and epigenetic alterations in late-passage hESCs compared to early-passage ones.
Main Methods:
- Comparison of paired early- and late-passage hESC lines.
- Analysis of genomic alterations including copy number, mitochondrial DNA sequence, and gene promoter methylation.
Main Results:
- Eight of nine late-passage hESC lines exhibited genomic alterations.
- Alterations included copy number aberrations (45%), mitochondrial DNA sequence changes (22%), and gene promoter methylation (90%).
- Methylation changes were primarily observed in 2 of 14 specific promoters.
Conclusions:
- hESC lines maintained in vitro accumulate genetic and epigenetic changes.
- Periodic monitoring of hESC lines is necessary for in vivo applications.
- Some late-passage hESC lines may not be suitable for therapeutic use due to genomic instability.