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Emily Singer

A View from Emily Singer

Biomedical News In Brief

A glitch for reprogrammed stem cells, a disease mystery solved, and a catalog of structural variations in the human genome.

  • February 3, 2011

A Glitch for Reprogrammed Stem Cells

Stem cells that have been reprogrammed from adult cells are demonstrably different than embryonic stem cells, which could throw into question their usefulness as a source of cell therapies.

The adult-derived cells, called induced pluripotent stem cells or iPS cells, are under intense study as a possible replacement for the more controversial embryonic stem cells because, like their embryonic cousins, they can differentiate into any type of tissue. But the first genome-wide comparison of the epigenetic modifications—chemical changes that modify how genes are expressed but do not change the genetic code itself—in iPS and embryonic stem cells found substantial diffefences.

According to the Los Angeles Times,

In a side-by-side comparison of these induced pluripotent stem cells and embryonic stem cells, researchers from the Salk Institute in San Diego found a consistent pattern of reprogramming errors — places where the iPS cells did not revert completely to an embryonic state.

Large regions of the iPS epigenomes hadn’t reverted to the embryonic state, but instead held on to the epigenetic memory of their tissue of origin. When the researchers used the iPS cells to create mature cells in the lab, this memory persisted.

The regions were clustered near telomeres and centromeres, structures that help direct how chromosomes divide.”There is something about these regions that makes it harder to modulate the epigenome,” Ecker said. In some ways the iPS cells were different from one another, suggesting the reprogramming process itself might contribute to aberrations, he added.

That does not mean iPS cells can’t be used in medicine, experts said. Improvements in technology could one day erase their epigenetic memory.

Scientists Discover a the Source of Rare Vascular Disease

A group of siblings with an extremely rare condition that causes calcium to build up in the arteries of the hands and legs finally has learned the source of their disorder; a faulty gene that normally protects arteries from calcifying. The finding is the first success for the National Institutes of Health’s Undiagnosed Diseases Program, which explores medical mysteries in patients from across the country.

While scientists have only found nine people with the disease to date, they say that what they learn from this rare condition will likely shed light on much more commons ones, such as heart disease, in which calcium builds up in coronary arteries.

According to an article in the New York Times, researchers are now working on treatments.

The simplest might be to give a bisphosphonate, an osteoporosis drug. With the gene mutation and decreased levels of adenosine, patients end up with high levels of an enzyme, alkaline phosphatase, needed to make calcium deposits. Bisphosphonates bring down levels of that enzyme.

Scientists Catalogue Large Variations in the Human Genome

Most analysis of the genetic differences from person to person have focused on single letter changes in the genome. But much larger structural variations, encompassing deletions, additions or inversions of tens to thousands of letters of DNA, likely play just as significant a role. Researchers across the globe have catalogued these variations more comprehensively than ever before, analyzing the genome sequencing of 185 people.

They found a total of 22,025 deletions and 6,000 other structural variants, according to a press release from Brigham and Women’s Hospital, one of the institutions involved in the project.

The study also provided important insights into how SVs are formed in the genome, thus linking SVs to mutational processes acting in the germline. “We found 51 hotspots where SVs, such as large deletions, appear to occur particularly often,” said Jan Korbel, PhD, a senior author of this study from the European Molecular Biology Laboratory in Heidelberg, Germany. “Six of those hotspots are in regions known to be related to genetic conditions, such as Miller-Dieker syndrome, a congenital brain disease that may lead to infant death.”

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