ESTOOLS - Advances with human embryonic stem cells - induced Pluripotent Stem Cells

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induced Pluripotent Stem Cells

Commentary & Research Note by Austin Smith and Peter Andrews

Stem cell research has been transformed by the discovery of Shinya Yamanaka and colleagues at Kyoto University that adult skin cells can be given the properties of embryonic stem cells by a simple genetic manipulation. This makes it likely that in the future the need to use supernumerary human embryos as a source of stem cells will be substantially reduced. First, however, it is essential to confirm that the induced pluripotent stem (iPS) cells created by the Yamanaka technique do indeed have the ability of embryonic stem cells to produce the complete repertoire of adult cell types. It is also necessary to develop methods of generating iPS cells that do not involve permanent genetic modification with the consequent risk of transformation into tumour cells. Continued comparative work with embryo derived cells will also be essential to exploit knowledge of pluripotent stem cells in understanding human development and the causes of birth defects. Researchers in ESTOOLS will contribute to these goals by rigorously comparing the properties of iPS cells and embryo-derived stem cells and by investigating alternative methods of creating iPS cells.

Link to Cell Press webpage with the full article by Yamanaka & colleagues, supplemental detail and other info

Research Note

Shinya Yamanaka and his colleagues first reported that mouse fibroblasts could be reprogrammed to an embryonic stem (ES) cell-like state by transfection with four genes, Oct4, Sox2, Klf4 and cMyc (1,2).  They suggested that these reprogrammed cells be called ‘induced Pluripotent Stem Cells’, or iPS cells.  Modifications to their original technique allowed them to produce germ-line competent iPS (3).  These results were confirmed in independent studies by Jaenisch and his colleagues (4).  Recently, Yamanaka and others have reported that similar techniques are also applicable to the production of human iPS cells from fetal and adult fibroblasts (5, 6, 7).  In the studies of Yamanaka, reprogramming was achieved by the same set of four genes as in the mouse (5), although his group found that reprogramming of human fibroblasts can also be achieved by omission of cMYC (7).  In their studies, Thomson and his colleagues found that re-programming was possible using OCT4, SOX2, NANOG and LIN28 (6). 

1. Takahashi K, Yamanaka S.  Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006 Aug 25; 126(4):663-76. Paper webpage
2. Lewitzky M, Yamanaka S.  Reprogramming somatic cells towards pluripotency by defined factors. Curr Opin Biotechnol. 2007 Oct; 18(5):467-73. Paper webpage
3. Okita K, Ichisaka T, Yamanaka S.  Generation of germline-competent induced pluripotent stem cells. Nature. 2007 Jul 19; 448(7151):313-7. Paper webpage
4. Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, Bernstein  BE, Jaenisch R.  In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature. 2007 Jul 19; 448(7151):318-24. Paper webpage
5. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S.  Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007 Nov 30; 131(5):861-72. Paper webpage
6. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie  J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA.  Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells. Science. 2007 Nov 20; [Epub ahead of print] PMID: 18029452 Paper webpage
7. Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, Okita K, Mochiduki Y, Takizawa N, Yamanaka S.  Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol. 2007 Nov 30; [Epub ahead of print] PMID: 18059259 Letter webpage