biotechnology

Mapping human stem cells’ mutant DNA

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Genetic changes take place in various human embryonic stem cells lines as they multiply in the laboratory, some of which resemble the DNA abnormalities typical of cancer cells. For the first time, researchers could shortlist a number of genes that map inside or near the mutated sites. Above, colonies of human embryonic stem cells (green) with feeder cells (dark red). (Courtesy: U. Sheffield)

U. SHEFFIELD (UK)—Scientists are closer to identifying and avoiding the adverse DNA changes that naturally occur when human embryonic stem cells are multiplied in the laboratory—changes that could hamper their future medical use.

The collaborative study, coordinated through an EU-funded project ESTOOLS and involving experts at the University of Sheffield, is published by the peer-review journal Nature Biotechnology.

Embryonic stem cells are studied for potential applications in regenerative cell replacement therapies because of their unique capacity to self-renew and  turn into a variety of cell and tissue types, including neurons, blood cells, bone, and muscle.

However, genetic changes take place in various human embryonic stem cells (hESCs) lines as they multiply in the laboratory, some of which resemble the DNA abnormalities typical of cancer cells.

The cells may also undergo other genetic changes undetectable by conventional methods, raising concerns about their potential medical use.

To address this issue, researchers used high-resolution DNA analysis to plot the genetic changes in 17 hESC lines cultured over many generations.

The study mapped hundreds of copy number variations (CNV) and loss of heterozigosity (LOH) after prolonged passages in culture. Both CNV and LOH are genetic variations that that may be associated with tumor transformation.

For the first time, researchers could shortlist a number of genes that map inside or near the mutated sites—and that could therefore be affected by these potentially deleterious changes.

“When we know which genes are involved, it will be easier to reject those hESC lines in which those genes are more likely to mutate,” says Peter Andrews, a professor in the biomedical science department at the University of Sheffield and a leading author of the study.

The authors point out that the study also will help to dig into the so-called culture adaptation process—the accumulation of genetic changes typical of malignant transformation that is mimicked by hESCs in culture—potentially providing clues to some of the genetic mechanisms underlying cancer development.

University of Sheffield news: www.shef.ac.uk/mediacentre/

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