November 28, 2011 -- Researchers from A*STAR Singapore took lead roles in a study that identified a portion of the genome mutated during long-term culture of human embryonic stem cells (hESCs). The study was a worldwide collaboration, led by Drs Peter Andrews of the University of Sheffield (UK), Paul Robson of the Genome Institute of Singapore (GIS), Steve Oh of Singapore’s Bioprocessing Technology Institute (BTI), and Barbara Knowles and others in the international stem cell community. The GIS, IMB and BTI are research institutes under the umbrella of the Agency for Science, Technology and Research, (A*STAR), Singapore.
Involving 125 ethnically diverse hESC lines originating from 38 laboratories globally, and now identified to represent multiple ethnic groups from different parts of the globe, the study is the largest to be conducted on the genetic stability of cultured hESCs. The findings are published today in the journal Nature Biotechnology.
Research into the variability of hESCs is very important as these cells may lead to future cell therapy and regenerative medicine. During long-term culture, however, these cells can acquire genetic changes (mutations), some of which could compromise the cells’ utility for regenerative medicine. It is believed that mutations that arise and endure over long-term culture provide a selective advantage for the cells, such as a greater propensity for self renewal.
The study re-emphasized that many chromosome changes occur repeatedly, resulting in increased copies in specific areas of the genome. Interestingly, through molecular karyotyping performed in Dr Robson’s laboratory at the GIS, about 20% of the karyotypically normal cell lines exhibited subkaryotypic amplifications of a specific region in chromosome 20. This is also one of the karyotypically defined areas of change. The minimal region common to these cells contains three ES-cell expressed genes, and one of them, BCL2L1, is a strong candidate for driving hESC culture adaptation. The data generated in this study will be useful for understanding the frequency and types of genetic changes affecting cultured hESCs, an important issue in evaluating the cells for potential therapeutic applications.