He started by trying to identify which genes were responsible for driving the development of embryonic cells. Then, he used engineered viruses that could infect cells (but no longer cause disease) to introduce these genes to adult cells; these, in turn, would instruct the cell to make the proteins that help the mature cells act more like embryonic ones. Yamanaka and his team winnowed 24 possible genes down to four.
Even Yamanaka was surprised that the process worked. When his colleague first showed him the older mouse cells that seemed to have reverted back to young versions of themselves, he refused to believe it. “I thought it was a mistake,” he says. “I asked my colleague to repeat the experiment again and again and again, but it always worked,” even with different types of mature mouse and human cells. “So we gradually became confident in the results.”
He called the cells induced pluripotent stem cells (iPS cells for short), and researchers raced to capitalize on the potential of these “Yamanaka factors” to generate replacements for diseased cells in conditions like diabetes and Parkinson’s disease. “iPS cells impact all sorts of areas, from the study of disease to the study of development,” says Dieter Egli, associate professor of developmental cell biology at Columbia University and a leading stem-cell scientist. “This fundamental insight of the reversion of time and cell specialization is absolutely a miracle.”
To capitalize on the discovery, the Japanese government invested heavily in CiRA—where the scientists’ teams still call him Yamanaka-sensei—to refine the production of iPS cells. One of the key genes involved in the process can also promote tumors; Yamanaka found a way to omit it while reprogramming the cells, albeit less efficiently, and has since developed ways to manufacture high-quality iPS cells for use in human studies. He also initiated important discussions with the government on the ethical use of these cells.
“When we succeeded in making human iPS cells, I was very happy for just one week,” Yamanaka says. The process bypassed the ethical challenges of needing embryos as a stem-cell source. “But I realized, ‘Wow, maybe I overcame one ethical hurdle, but now I generated another, even higher hurdle.’”
Read the full article here
