iPSC reprogramming (Yamanaka)

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Kazutoshi Takahashi and Shinya Yamanaka, Kyoto University. Yamanaka shared the 2012 Nobel Prize in Physiology or Medicine equally with John Gurdon "for the discovery that mature cells can be reprogrammed to become pluripotent" (able to become any cell type).

What happened

• 2006 (mouse). Starting from 24 candidate genes, the team found that four (Oct3/4, Sox2, c-Myc and Klf4) could convert mouse embryonic and adult fibroblasts (connective-tissue cells) into induced pluripotent stem cells (iPSCs). These looked and grew like embryonic stem cells, formed tumours containing tissue from all three germ layers when transplanted into nude mice, and contributed to embryonic development when injected into blastocysts. Cell 126:663–676, published online 10 Aug 2006. The authors noted it was unproven in human cells and that c-Myc might be unsuitable for clinical use.
• 2007 (human). The same four factors reprogrammed adult human skin fibroblasts (Takahashi, Tanabe, Ohnuki, Narita, Ichisaka, Tomoda, Yamanaka), giving cells similar to human embryonic stem cells that made all three germ layers in vitro and in teratomas. Cell 131:861–872, 30 Nov 2007.
• Human, second route (2007). J. A. Thomson's group reported human iPSCs made with a different set of four factors (OCT4, SOX2, NANOG, LIN28) the same month (Yu et al., Science 318:1917–1920).
• 2009 (Parkinson's). Jaenisch's lab at the Whitehead Institute, with O. Isacson, made iPSCs from skin cells of five people with idiopathic Parkinson's, turned them into dopamine neurons, and made versions free of the reprogramming genes (Soldner et al., Cell 136:964–977).
• 2011 (inherited forms). iPSC lines carrying LRRK2 G2019S (Nguyen et al., Cell Stem Cell 8:267–280; their dopamine neurons showed more oxidative-stress genes and more synuclein) and an SNCA triplication (Devine et al., Nat Commun 2:440).

Correction to the candidate list: "2006" is right for the mouse work, but the human result that matters for Parkinson's is 2007, so the file covers both.

Why it moved us toward a cure

It created two routes. One is "disease in a dish": neurons grown from a patient's own cells to study the disease and screen drugs. The other is cell replacement without embryos: the neurons grafted in landmark 30 and the Kyoto trial in landmark 10 come from iPSCs, using the differentiation recipe of landmark 17.

Outcome

Advanced. The Kyoto trial led to Japan's conditional approval in March 2026 (see landmark 300), which is the first clinical use of the idea in Parkinson's.

Sources

• Takahashi & Yamanaka, Cell 2006;126:663–676, DOI 10.1016/j.cell.2006.07.024, PMID 16904174 (abstract via PubMed; the 24-gene screen and the c-Myc caution are from a copy of the paper) · ScienceDaily, 11 Aug 2006
• Takahashi et al., Cell 2007;131:861–872, DOI 10.1016/j.cell.2007.11.019, PMID 18035408 · Yu et al., Science 2007;318:1917–1920, DOI 10.1126/science.1151526, PMID 18029452
• Soldner et al., Cell 2009;136:964–977, DOI 10.1016/j.cell.2009.02.013, PMID 19269371 · MIT repository copy · Nguyen et al., Cell Stem Cell 2011;8:267–280, DOI 10.1016/j.stem.2011.01.013 · Devine et al., Nat Commun 2011;2:440, DOI 10.1038/ncomms1453 · ScienceDaily, Mar 2009
• Nobel Prize 2012 summary
• Not yet verified: the number of candidate genes (24) and the c-Myc caution, which rest on a copy of the paper; whether Nguyen 2011 and Devine 2011 were the first LRRK2 and SNCA iPSC reports; the Nobel citation was taken from a search summary of the Nobel Prize page (the page itself blocked reading); that the Kyoto cells were made by the recipe in landmark 17 (as stated in earlier landmarks, not re-checked here).