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A embo j 16 65106520 1997 reprogramming viewed as

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Unformatted text preview: •  SomaKc cell nuclear transfer (SCNT) to a donor oocyte followed by in vitro ferKlizaKon and culture, and producKon of ESCs. •  DerivaKves of the ESCs can be used for the producKon of cells from the individual. •  The ethics of therapeuKc cloning and use of embryos for ESC generaKon in general remains a mager of considerable debate and is illegal in many countries and US states. Cell Fusion Reprogramming •  Fusion of two cells leads to gene acKvity of dominant cell type: •  Tada, Surani and colleagues showed that ES cells and embryonic germ cells contain factors that can induce reprogramming and pluripotency in somaKc cells Somatic cell Adult cell types Tada, M., Tada, T., Lefebvre, L., Barton, S. C. & Surani, M. A. EMBO J. 16, 6510–6520 (1997). Reprogramming Viewed as ManipulaKon of the EpigeneKc Landscape 4 4/18/13 Reprogramming of SomaKc Cells By Minimal Sets of TranscripKon Factors •  •  •  •  AusKn Smith and others, including Shinya Yamanaka, found a number of transcripKon factors to be enriched in pluripotent cells. These factors were necessary to maintain pluripotency  ­ ­ but not individually sufficient to achieve the pluripotent state. Yamanaka, 2006, systemaKcally evaluated combinaKons of factors (24 factors) and eventually found that 4 (Oct4, Sox2, c ­myc and KLF4) would produce pluripotent cells that gave limited chimerism upon transplantaKon into blastocysts, but no germline transmission Yamanaka and Rudy Jaenisch in 2007 independently achieved germline transmission in mice. Yamanaka (Oct4, Sox2, c ­myc, KLF4) and Thomson (Oct4, Sox2, LIN28, Nanog) achieved human somaKc cell reprogramming Keisuke Okita, Tomoko Ichisaka & Shinya Yamanaka Vol 448| 19 July 2007| doi:10.1038/nature...
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