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Biologists develop efficient genetic modification of human embryonic stem cells
Date:1/7/2010

uccessfully transferred a defective copy of the gene p53, which suppresses cancer, into a human embryonic stem cell line. By repeating the process in a second round, they developed a line of cells in which both copies of the genes were disrupted.

They also report success with a different gene, ATM, which when mutated in humans causes Ataxia-telangiectasia, a disease characterized by a host of systemic defects including increased cancer risk, degeneration of specific types of brain cells and degraded telomeres, the protective caps at the end of each chromosome.

Genetically engineered mice with two bad copies of the ATM gene share some of these traits with human patients, but not all. Neurons don't degenerate in ATM mice, for example, and the telomeres are long. "If you want to study accelerated shortening of telomeres, you can't do it in the mouse. You can only do it in human cells," Xu said.

Those differences propelled Xu's group to develop human cell lines instead, with the hope that some of the processes that go wrong in human patients could be studied in the lab. Already, they have demonstrated that their ATM-deficient embryonic stem cell line has damaged telomeres. Other characteristics, such as the degeneration of specific types of neurons, will be the subject of future experiments, Xu said.

The authors say their approach can easily be adapted to modify other human genes within other stem cells lines. For their initial work, Xu's group used a cell line that easily forms new colonies from single cells, but they also repeated the procedure in a cell line called H9, which has proved difficult to manipulate.

Because H9 was among the few cells lines approved for use by researchers funded by the federal government before new lines began to be approved in mid-December 2009, many researchers already have considerable experience with coaxing the cells into differentiating into specific types of tissues, for example, which w
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Contact: Yang Xu
scinews@ucsd.edu
University of California - San Diego
Source:Eurekalert

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