Tag Archives: Yamanaka

The 2012 Nobel Prize in Physiology or Medicine

Yesterday, the Nobel committee in Stockholm announced that the 2012 Prize in Physiology or Medicine would be going to John B. Gurdon and Shinya Yamanaka for the discovery that adult, differentiated cells could be de-differentiated again into pluripotent cells.

In countries where research on embryonic stem cells is essentially frozen — like Japan, for instance — this variety of pluripotent cells could prove to be a boon. More importantly, experiments done by these men revolutionized our understanding of the cellular lifecycle; no longer was it unidirectional, where cells moved down a one-way path into specialization.

I especially liked SciAm’s profile of Yamanaka’s work. His research showed that a bare handful of genes — four, to be precise — could turn back cellular time and ‘regress’ the cell into its pluripotent state.

…[Yamanaka]uncovered 24 factors that, when added to ordinary mouse fibroblast cells and subjected to the correct culturing procedures, could create pluripotent cells virtually identical to stem cells. Yamanaka kept examining each factor and found that none could do the job alone; instead a combination of four particular genes did the trick.

Note the “virtually identical” in that paragraph.

Yamanaka and others do not think that iPS cells can replace their embryonic counterparts yet. “We don’t yet know if embryonic stem cells and iPS cells are truly equivalent,” says Konrad Hochedlinger of Massachusetts General Hospital’s Center for Regenerative Medicine.

There are other issues with pluripotent cells: they need to be injected with some kind of retrovirus, which would leave the new cells full of the potential to attack our immune system. They’ve been working on this, however, and now Yamanaka’s team has come up with a way to use a circular, double stranded round of DNA called plasmids to replace retroviruses.

Yamanaka’s lab reported success using plasmids, or circular pieces of DNA. Other retrovirus alternatives include proteins and lipid molecules.

The risks don’t end there. Since one of the genes that controls the induction of pluripotency is strongly cancerous, there’s a chance that the stem cells could become tumorous too. There’s still hope, though:

…the transcription factor c-Myc happens to be a powerful cancer gene, and the cells produced by Yamanaka’s team tended to become cancerous. “Making iPS cells is very similar to making cancer,” he explains. In principle, c-Myc may not be necessary: in mice, Yamanaka and a group led by Rudolf Jaenisch at the Massachusetts Institute of Technology found a way to avoid using c-Myc, in part, by optimizing culture conditions.