Researchers examine human embryonic stem cell genome

Mar 27, 2008

Stem cell researchers from UCLA used a high resolution technique to examine the genome, or total DNA content, of a pair of human embryonic stem cell lines and found that while both lines could form neurons, the lines had differences in the numbers of certain genes that could control such things as individual traits and disease susceptibility.

The technique used to study the genome, which contains all the genes on 46 chromosomes, is called array CGH. The use of higher resolution techniques, such as array CGH and, soon, whole genome sequencing, will enhance the ability of researchers to examine stem cell lines to determine which are best – least likely to result in diseases and other problems – to use in creating therapies for use in humans.

Array CGH provided a much better look at the gene content on the chromosomes of human embryonic stem cells, with a resolution about 100 times better than standard clinical methods. Clinical specialists commonly generate a karyotype to examine the chromosomes of cancer cells or for amniocentesis in prenatal diagnosis, which has a much lower resolution than Array CGH, said Michael Teitell, a researcher with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research and the senior author of the study. Small defects that could result in big problems later on could be missed using karyotyping for stem cells.

“Basically, this study shows that the genetic makeup of individual human embryonic stem cell lines is unique in the numbers of copies of certain genes that may control traits and things like disease susceptibility,” said Teitell, who also is an associate professor of pathology and laboratory medicine and a researcher at UCLA’s Jonsson Comprehensive Cancer Center. “So, in choosing stem cell lines to use for therapeutic applications, you want to know about these differences so you don’t pick a line likely to cause problems for a patient receiving these cells.”

The study appears in the March 27, 2008 express edition of the journal Stem Cells.

Differences between individual DNA sequences provide the basis for human genetic variability. Forms of variation include single DNA base pair alterations, duplications or deletions of genes or sets of genes, and translocations, a chromosomal rearrangement in which a segment of genetic material from one chromosome becomes heritably linked to another chromosome. These changes can be benign, but they can also promote diseases such as certain cancers, or confer increased risk to other diseases, such as HIV infection or certain types of kidney ailments.

In this study, Teitell and his team sought to determine copy number variants (CNVs), or differences in the numbers of certain genes, in two embryonic stem cell lines. The CNVs provide a unique genetic fingerprint for each line, which can also indicate relatedness between any two stem cell lines. Teitell used embryonic stem cell lines that made different types of neurons and studied them with array CGH for comparison. His team found CNV differences between the two lines in at least seven different chromosome locations below the level of detection using standard karyotype studies. Such differences could impact the therapeutic utility of the lines and could have implications in disease development. More studies will be required to determine the effect of specific CNVs in controlling stem cell function and disease susceptibility, he said.

“In studying embryonic stem cell lines in the future, if we find differences in regions of the genome that we know are associated with certain undesirable traits or diseases, we would choose against using such stem cells, provided safer alternative lines are available,” Teitell said.

Large genome-wide association studies are underway in a variety of diseases to determine what genetic abnormalities might be at play. When the genetic fingerprint or predisposing genes for a certain disease is discovered, it could be used as key information in screening embryonic stem cell lines.

Source: University of California - Los Angeles

Explore further: Italian olive tree disease stumps EU

add to favorites email to friend print save as pdf

Related Stories

A single-cell breakthrough

Mar 18, 2015

The human gut is a remarkable thing. Every week the intestines regenerate a new lining, sloughing off the equivalent surface area of a studio apartment and refurbishing it with new cells. For decades, researchers ...

Nano packages for anti-cancer drug delivery

Mar 18, 2015

Cancer stem cells are resistant to chemotherapy and consequently tend to remain in the body even after a course of treatment has finished, where they can often trigger cancer recurrence or metastasis. A new ...

Vaccines from a reactor

Mar 02, 2015

In the event of an impending global flu pandemic, vaccine production could quickly reach its limits, as flu vaccines are still largely produced in embryonated chicken eggs. Udo Reichl, Director at the Max ...

Recommended for you

Italian olive tree disease stumps EU

2 hours ago

EU member states are divided on how to stop the spread of a disease affecting olive trees in Italy that could result in around a million being cut down, officials said Friday.

China starts relocating endangered porpoises: Xinhua

8 hours ago

Chinese authorities on Friday began relocating the country's rare finless porpoise population in a bid to revive a species threatened by pollution, overfishing and heavy traffic in their Yangtze River habitat, ...

A long-standing mystery in membrane traffic solved

9 hours ago

In 2013, James E. Rothman, Randy W. Schekman, and Thomas C. Südhof won the Nobel Prize in Physiology or Medicine for their discoveries of molecular machineries for vesicle trafficking, a major transport ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

herpesdate
not rated yet Apr 02, 2008
Share this with HIV people at www.STDromance.com

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.