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UCLA researchers examine human embryonic stem cell genome
March 28, 2008Stem 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.
University of California - Los Angeles
"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.
University of California - Los Angeles
Stem Cell Current Events and Stem Cell News RSSNew discovery about the formation of new brain cells
The generation of new nerve cells in the brain is regulated by a peptide known as C3a, which directly affects the stem cells' maturation into nerve cells and is also important for the migration of new nerve cells through the brain tissue, reveals new research from the Sahlgrenska Academy published in the journal Stem Cells.
Gene mismatch influences success of bone marrow transplants
A commonly inherited gene deletion can increase the likelihood of immune complications following bone marrow transplantation, an international team of researchers reports in the November 22 advance online issue of Nature Genetics.
New research shows versatility of amniotic fluid stem cells
For the first time, scientists have demonstrated that stem cells found in amniotic fluid meet an important test of potential to become specialized cell types, which suggests they may be useful for treating a wider array of diseases and conditions than scientists originally thought.
First reconstitution of an epidermis from human embryonic stem cells
Stem cell research is making great strides. This is yet again illustrated by a study carried out by the I-STEM* Institute (I-STEM/ Inserm UEVE U861/AFM), published in the Lancet on 21 November 2009. The I-STEM team, directed by Marc Peschanski has just succeeded in recreating a whole epidermis from human embryonic stem cells.
Your Own Stem Cells Can Treat Heart Disease
The largest national stem cell study for heart disease showed the first evidence that transplanting a potent form of adult stem cells into the heart muscle of subjects with severe angina results in less pain and an improved ability to walk. The transplant subjects also experienced fewer deaths than those who didn't receive stem cells.
U of M researchers find 2 units of umbilical cord blood reduce risk of leukemia recurrence
A new study from the Masonic Cancer Center, University of Minnesota shows that patients who have acute leukemia and are transplanted with two units of umbilical cord blood (UCB) have significantly reduced risk of the disease returning.
Researchers find potential treatment for Huntington's disease
Investigators at Burnham Institute for Medical Research (Burnham), the University of British Columbia's Centre for Molecular Medicine and Therapeutics and the University of California, San Diego have found that normal synaptic activity in nerve cells (the electrical activity in the brain that allows nerve cells to communicate with one another) protects the brain from the misfolded proteins associated with Huntington's disease.
Researchers 'notch' a victory toward new kind of cancer drug
Scientists have devised an innovative way to disarm a key protein considered to be "undruggable," meaning that all previous efforts to develop a drug against it have failed.
UCI embryonic stem cell therapy restores walking ability in rats with neck injuries
The first human embryonic stem cell treatment approved by the FDA for human testing has been shown to restore limb function in rats with neck spinal cord injuries - a finding that could expand the clinical trial to include people with cervical damage.
First use of antibody and stem cell transplantation to successfully treat advanced leukemia
For the first time, researchers at Fred Hutchinson Cancer Research Center have reported the use of a radiolabeled antibody to deliver targeted doses of radiation, followed by a stem cell transplant, to successfully treat a group of leukemia and pre-leukemia patients for whom there previously had been no other curative treatment options.
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