High-res technology shows significant differences in stem cell lines
By Kim Irwin| 4/2/2008
UCLA stem cell researchers using a high-resolution technique to
examine the genome of a pair of human embryonic stem cell lines have
found that while both lines could form neurons, they differed in the
numbers of certain genes that could control such things as individual
traits and disease susceptibility.
The study appears in the April issue of the peer-reviewed journal
Stem Cells.
The researchers used a technique known as array CGH (comparative
genomic hybridization) to study the total DNA content of the lines,
all the genes on 46 chromosomes. The use of higher-resolution
techniques like array CGH and, soon, whole-genome sequencing will
enhance the ability of researchers to examine stem cell lines to
determine which are best — or least likely to result in diseases and
other problems — for creating therapies for use in humans.
Array CGH provided a much better look at the gene content on the
chromosomes, with a resolution about 100 times better than standard
clinical methods. Clinical specialists commonly generate a karyotype —
a technique involving the staining and photographing of a cell
sample — to examine the chromosomes of cancer cells or for
amniocentesis in prenatal diagnosis; karyotyping 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 at UCLA 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,
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."
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 — chromosomal rearrangements 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
the 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 — differences that could not
have been detected 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.
UCLA's stem cell center was launched in 2005 with a UCLA commitment
of $20 million over five years. A $20 million gift from the Eli and
Edythe Broad Foundation in 2007 resulted in the renaming of the
center.
The Eli and Edythe Broad Center of Regenerative Medicine and Stem
Cell Research at UCLA, with more than 150 members, is committed to a
multidisciplinary, integrated collaboration of scientific, academic
and medical disciplines for the purpose of understanding adult and
human embryonic stem cells. The institute supports innovation,
excellence and the highest ethical standards focused on stem cell
research with the intent of facilitating basic scientific inquiry
directed towards future clinical applications to treat disease. The
center is a collaboration of the David Geffen School of Medicine at
UCLA, UCLA's Jonsson Comprehensive Cancer Center, the UCLA Henry
Samueli School of Engineering and Applied Science, and the UCLA
College of Letters and Science. To learn more about the center, visit
www.stemcell.
http://newsroom.
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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