Induced pluripotent stem (iPS)cells

Patient-Specific Pluripotent Stem Cells

Nuclear reprogramming to a pluripotent state by three approachesShinya Yamanaka & Helen M. BlauNATURE|Vol 465|10 June 2010|doi:10.1038/nature09229

The fusion experiments by Tada, Surani and colleaguesclearly showed that ES cells and embryonic germ cellscontain factors that can induce reprogramming and pluripotencyin somatic cells*.

Before 2006, the prevailing view was that nuclear reprogramming to a pluripotent state is a highly complex process that might entail the cooperation of up to 100 factors**.

*Tada, M., Tada, T., Lefebvre, L., Barton, S. C. & Surani, M. A. Embryonic germ cells induce epigenetic reprogramming of somatic nucleus in hybrid cells. EMBO J. 16, 6510–6520 (1997).

**Nuclear reprogramming to a pluripotent state by three approachesShinya Yamanaka & Helen M. BlauNATURE|Vol 465|10 June 2010|doi:10.1038/nature09229

Nuclear reprogramming to a pluripotent state by three approachesShinya Yamanaka & Helen M. BlauNATURE|Vol 465|10 June 2010|doi:10.1038/nature09229

Induction of Pluripotent Stem Cells from Mouse Embryonic and AdultFibroblast Cultures by Defined FactorsKazutoshi Takahashi and Shinya YamanakaCell 126, 663–676, August 25, 2006

b-geo cassette (a fusion of the b-galactosidaseand neomycin resistance genes) 24 genes

Morphology: 5/12 survived

Oct3/4, Klf4, Sox2, and c-Myc

Induction of Pluripotent Stem Cells from Mouse Embryonic and AdultFibroblast Cultures by Defined FactorsKazutoshi Takahashi and Shinya YamanakaCell 126, 663–676, August 25, 2006

Gene-Expression Profiles of iPS Cells

Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined FactorsKazutoshi Takahashi and Shinya YamanakaCell 126, 663–676, August 25, 2006

Pluripotency of iPS Cells Derived from MEFs

Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined FactorsKazutoshi Takahashi and Shinya YamanakaCell 126, 663–676, August 25, 2006

they are different with regards to gene expression and DNA methylation patterns, and fail to produce adult chimaeras.

Generation of germline-competent induced pluripotent stem cellsKeisuke Okita, Tomoko Ichisaka & Shinya YamanakaVol 448| 19 July 2007| doi:10.1038/nature05934

Induction of Pluripotent Stem Cells from Adult Human Fibroblastsby Defined FactorsKazutoshi Takahashi, Koji Tanabe, Mari Ohnuki, Megumi Narita, Tomoko Ichisaka, Kiichiro Tomoda, and Shinya Yamanaka1,2

The generation of iPS cells from adult human dermal fibroblasts with the same four factors: Oct3/4, Sox2, Klf4, and c-Myc.

Human iPS cells were similar to human embryonic stem (ES) cells in morphology, proliferation, surface antigens, gene expression, epigenetic status of pluripotent cell-specific genes, and telomerase activity. Furthermore, these cells could differentiate into cell types of the three germ layers in vitro and in teratomas.

These findings demonstrate that iPS cells can be generated from adult human fibroblasts.

Suppression of induced pluripotent stem cell generation by the p53–p21 pathwayHyenjong Hong, Kazutoshi Takahashi, Tomoko Ichisaka, Takashi Aoi, Osami Kanagawa, Masato Nakagawa, Keisuke Okita & Shinya YamanakaVol 460|27 August 2009| doi:10.1038/nature08235

Up to 10% of transduced mouse embryonic fibroblasts lacking p53 became iPS cells, even without the Myc retrovirus. The p53 deletion also promoted the induction of integration-free mouse iPS cells with plasmid transfection.

Furthermore, in the p53-null background, iPS cells were generated from terminally differentiated T lymphocytes. The suppression of p53 also increased the efficiency of humaniPS cell generation.

Nuclear reprogramming to a pluripotent state by three approachesShinya Yamanaka & Helen M. BlauNATURE|Vol 465|10 June 2010|doi:10.1038/nature09229

Timeline of discoveries in nuclear reprogramming.Nuclear reprogramming to a pluripotent state by three approachesShinya Yamanaka & Helen M. BlauNATURE|Vol 465|10 June 2010|doi:10.1038/nature09229

Shinya Yamanaka, Professor of Kyoto University, won the Albert Lasker Basic Medical Research Award in 2009.

Often referred to as “America’s Nobel,” the Lasker Award is one of the most prestigious scientific awards.