Navigation Links
Biologists develop efficient genetic modification of human embryonic stem cells

Biologists have developed an efficient way to genetically modify human embryonic stem cells. Their approach, which uses bacterial artificial chromosomes to swap in defective copies of genes, will make possible the rapid development of stem cell lines that can both serve as models for human genetic diseases and as testbeds on which to screen potential treatments, they say.

"This will help to open up the whole human embryonic stem cell field. Otherwise, there's really few efficient ways you can study genetics with them," said Yang Xu, professor of biology at the University of California, San Diego who directed the research. Xu and co-authors Hoseok Song and Sun-Ku Chung, both postdoctoral fellows in Xu's research group, describe their technique in the January 8 issue of the journal Cell Stem Cell.

Most attempts to alter the genetic makeup of the cells have proved too inefficient, Xu said. His group used bacterial artificial chromosomes, or BACs, to improve the yield.

BACs are synthesized circles of human DNA, which bacteria will replicate just like their own native chromosomes. Commercially available BACs can be modified within bacterial cells to insert altered copies of specific genes. Once the modified BACs are introduced into human cells, they will sometimes pair up with a matching segment of a human chromosome and swap segments of DNA, a process called homologous recombination.

The advantage of using BACS to alter the genetic code in human cells comes from the long flanking sequences on either side of the modified gene, which increases the chance that the BAC with line up with native DNA in position for a swap. Other genetic approaches have been limited by shorter segments of DNA.

Using BACs, the team was able to substitute modified genes in 20 percent of treated cells. Standard methods of genetic modification typically achieve modification in fewer than one percent of cells, Xu said.

His group successfully 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 would make the ability to genetically modify them particularly valuable.


Contact: Yang Xu
University of California - San Diego

Related medicine news :

1. Biologists Question Animal Brain Size Theory
2. Where tumor cells boldly go: Weill Cornell cancer biologists shed light on the metastatic niche
3. Cell biologists identify new tumor suppressor for lung cancer
4. Microbiologists receive top Canadian recognition
5. Boston College biologists build a better mouse model for cancer research
6. Biologists Discover How Dengue Virus Matures
7. FDA clears TransOral robotic surgery developed at Penn
8. Michael J. Fox Foundation Awards $1 Million for Critical Step Toward Development of Dyskinesia Treatments
9. Nu-Tek Products Develops Cultured Soymilk Powder
10. Milton & DeKruif Launches New Client Development Campaign
11. Safety and Quality Software Developer Quantros, Inc. Launches Healthcare IT Consulting Division
Post Your Comments:
(Date:12/1/2015)... ... December 01, 2015 , ... ... it has been awarded a fixed price per sprint agile development contract to ... at $34 million over five years, provides software engineering, infrastructure, as well as ...
(Date:12/1/2015)... ... December 01, 2015 , ... TCS Healthcare Technologies (TCS), a ... health arenas, is pleased to announce that VIP Care Services, a Caprock Health ... the ACUITY Complete Care™ Management to back their collaborative catastrophic case management initiatives. ...
(Date:12/1/2015)... ... ... XTC Semifinals 2016 - CES, Las Vegas, Nevada - Extreme ... 2016, the world’s largest Consumer Electronic Show, where they will present to a panel ... Pacific Investments Veronica Serra, and venture capitalist Tim Draper among many other top names ...
(Date:12/1/2015)... Aliso Viejo, CA (PRWEB) , ... December 01, 2015 , ... ... any length of footage, and with full control over customization, the possibilities are truly ... color, frame rate, position randomization, overlay depth position, vertical flip, horizontal flip, depth of ...
(Date:12/1/2015)... CA (PRWEB) , ... December 01, 2015 , ... ... Modern Luxury’s Angeleno Magazine as a Modern Man for 2015. , Angeleno ... publisher in the United States. Established in 1994, Modern Luxury includes more than ...
Breaking Medicine News(10 mins):
(Date:12/1/2015)... Dec. 1, 2015  AccuTEC Blades, a leader ... corporate logo and brand identity program. The new ... engineering of bladed products where "the edge makes ... --> Serving manufacturers and distributors of ... glass equipment, AccuTEC,s product lines include those acquired ...
(Date:12/1/2015)... Dec. 1, 2015  Six months of adjunctive metformin therapy ... 1 diabetes, according to new research from T1D Exchange ... may have a beneficial effect on measures of obesity, including ... of the Journal of the American Medical Association , ... effect of metformin on overweight and obese adolescents with type ...
(Date:12/1/2015)... During the recent 2015 Transcatheter Cardiovascular ... CA , Medinol Ltd. continued to introduce ... a satellite symposium, "The BioNIR eDES: The Role ... a renowned physician panel discussed the key attributes ... Stent System and the Medinol eDES Coronary Stent ...
Breaking Medicine Technology: