|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.”Amy Adams