How it began
Shinya Yamanaka, born in Osaka in 1962 and a professor at Kyoto University, studied embryonic stem cells and looked for the genes that kept them immature. He and his co-workers introduced such genes, in different combinations, into fibroblasts, mature cells from the connective tissue of mice. They found a combination that worked, and the recipe was surprisingly simple. The result was published in 2006 by Kazutoshi Takahashi and Yamanaka in the journal Cell and was at once regarded as a major breakthrough.
Before it existed
It was long thought that a cell changes during maturation in such a way that it can no longer return to an immature, pluripotent stage. In 1962 John Gurdon showed that specialization is reversible, by replacing the nucleus of a frog egg cell with the nucleus of a mature intestinal cell and obtaining a normal tadpole. Whether an intact mature cell could be fully reprogrammed remained unknown.
How it works
Yamanaka began with 24 candidate genes active in embryonic stem cells and narrowed them down. Four transcription factors, Myc, Oct3/4, Sox2 and Klf4, were enough to convert mouse fibroblasts into pluripotent stem cells. The resulting induced pluripotent stem cells, or iPS cells, could develop into mature cell types such as fibroblasts, nerve cells and gut cells.
What changed first
In 2007 Yamanaka and his colleagues were the first to produce human iPS cells. Yamanaka developed the method as an alternative to embryonic stem cells, avoiding an approach in which embryos would be destroyed. In 2012 he and Gurdon shared the Nobel Prize in Physiology or Medicine for the discovery that mature cells can be reprogrammed to become pluripotent.
Where it stands today
Yamanaka directs the Center for iPS Cell Research and Application at Kyoto University. Open problems noted on Wikipedia include the very low rate at which iPS cells are produced and the fact that the four factors have been shown to be oncogenic. In 2013 iPS cells were used in Japan to generate a vascularized, functional human liver in mice.
