Study: Human Embryonic Stem Cells Acquire Mutations From Long-Term Culture

A large international stem cell collaboration has identified a portion of the genome mutated during long-term culture of human embryonic stem cells.

AsianScientist (Nov. 28, 2011) – A large international stem cell collaboration has identified a portion of the genome mutated during long-term culture of human embryonic stem cells (hESCs).

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 researchers published their findings today in the journal Nature Biotechnology.

The study, which involved 125 ethnically diverse hESC lines originating from 38 laboratories globally, and representing multiple ethnic groups from different parts of the globe, is the largest to be conducted on the genetic stability of cultured hESCs.

hESCs, which are believed to be the key to future cell therapy and regenerative medicine, can acquire genetic changes (mutations) during long-term culture, some of which could compromise the cells’ utility for regenerative medicine.

Scientists believe that these mutations provide a selective advantage for the cells, such as a greater propensity for self renewal, a characteristic associated with cancer cells.

The study showed that these mutational changes occur frequently; molecular karyotyping showed that about 20 percent of the karyotypically normal cell lines exhibited subkaryotypic amplifications of a specific region in chromosome 20. Common to these cells is a minimal region containing three ES-cell expressed genes, and one of them, BCL2L1, is a strong candidate for driving hESC culture adaptation.

“This same region has recently been identified to repeatedly occur in numerous human cancer cell types, this likely indicative of similar selection pressures at play in stem cells and cancer cells,” said Dr Paul Robson, Senior Group Leader of the Developmental Cellomics Laboratory, GIS, where the finding was made.

“Interestingly, we found the propensity for mutation at this location is associated with a relatively recent chromosomal rearrangement that occurred in the last common ancestor of the human, chimp, and gorilla thus pointing to the value of having a comparative perspective for understanding human biology,” he said.

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.

The article can be found at: The International Stem Cell Initiative (2011) Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage.


Source: A*STAR.
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