Thursday, November 14, 2013

Gladstone Institutes scientists overcome a barrier in generating iPS cells

These fibroblasts are currently in the process of being reprogrammed into iPS cells. The activation of LIN-41 (shown in green) has helped remove a molecular barrier that prevented efficient reprogramming. [image: Kathleen Worringer]

You'd think that after winning a Nobel Prize, Shinya Yamanaka would be ready to leave his discovery well enough alone. He's the scientist who, in 2007, showed that it's possible to convert human skin cells back into a cell that mimics embryonic stem cells (called iPS cells). They can mature into all the cell types of the body.

But the problem remains that his technique isn't very efficient. Only about one out of every 100 skin cells gets reprogrammed into an iPS cell. He and others have been working to find more efficient ways to prod the cells' transformation.

Yamanaka, who is a Gladstone Institutes Investigator, worked with CIRM training grant recipient Kathleen Worringer to find a way of improving the efficiency of the technique. They published their results in the November 14 issue of Cell Stem Cell.

The exact details of what they found are a veritable alphabet soup of gene and protein names. Suffice it to say that they added something new to the mix, and it helped.

They had some clues that this new factor might be effective, and it was, but it took some molecular sleuthing to understand how and why. It turns out that the factor in question has nothing to do with reprogramming. Instead it kicks off a domino effect of proteins that activate genes that make proteins that turn off other genes. In the end, a gene celled EGR1 gets turned off, and that's what improves reprogramming. 

The Gladstone Institutes wrote a good story about the work that goes into more of the scientific nitty gritty, for those hoping to learn more.

The Gladstone Institutes quote Yamanaka about the importance of these results:
“Ever since we first described our ability to generate iPS cells, we’ve been searching for ways to improve upon it. Our results represent one very important step towards that goal.” 
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1 comment:

  1. A WSJ special project: A group of parents and scientists is racing to find a cure for the rare genetic disease that is killing children. Their collaboration is pushing the boundaries of medical research.

    The couple discovered online a small community of families, researchers and doctors linked by NPC disease. Ms. Hempel created a blog to post medical updates about her girls and to share scientific papers. She tapped into a stream of discontent flowing through chat groups and patient sites, complaints that science moved too slowly to keep up with the symptoms progressing in loved ones.

    The Hempels learned of people who called themselves citizen-scientists. Many shared research papers and their day-to-day experience. Some talked of their willingness to try any promising drug. Others sought a role as equal partners with researchers.

    Scientists, while sympathetic, generally believe their work should be left to experts. Families are encouraged to raise money if they want to help, but the traditional view is that amateurs can't shape research or find cures.

    The Hempels found a maddening gap between the search for scientific knowledge and the search for treatments.

    Scientists aren’t villains, Ms. Hempel said, but too many are hobbled by secrecy and rigid tradition. “The bottom line is their work does not translate fast enough to help Addi and Cassi and the other NPC kids,” she said.

    To change that, the Hempels needed to find allies.