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Reprogramming of human somatic cells to pluripotency with defined factors

Nature volume 451, pages 141146 (10 January 2008) | Download Citation

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Abstract

Pluripotency pertains to the cells of early embryos that can generate all of the tissues in the organism. Embryonic stem cells are embryo-derived cell lines that retain pluripotency and represent invaluable tools for research into the mechanisms of tissue formation. Recently, murine fibroblasts have been reprogrammed directly to pluripotency by ectopic expression of four transcription factors (Oct4, Sox2, Klf4 and Myc) to yield induced pluripotent stem (iPS) cells. Using these same factors, we have derived iPS cells from fetal, neonatal and adult human primary cells, including dermal fibroblasts isolated from a skin biopsy of a healthy research subject. Human iPS cells resemble embryonic stem cells in morphology and gene expression and in the capacity to form teratomas in immune-deficient mice. These data demonstrate that defined factors can reprogramme human cells to pluripotency, and establish a method whereby patient-specific cells might be established in culture.

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Gene Expression Omnibus

Data deposits

The microarray data have been deposited in GEO and given the series accession number GSE9832.

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Acknowledgements

This research was funded by grants from the National Institutes of Health (NIH) and the NIH Director’s Pioneer Award of the NIH Roadmap for Medical Research, and made possible through the generosity of Joshua and Anita Bekenstein. G.Q.D. is a recipient of the Burroughs Wellcome Fund Clinical Scientist Award in Translational Research.

Author Contributions I.-H.P. (project planning, experimental work, preparation of manuscript); R.Z., J.A.W., A.Y., H.H., P.H.L. (experimental work); T.A.I. (interpretation of teratoma pathology); M.W.L. (experimental work, preparation of manuscript); G.Q.D. (project planning, preparation of manuscript).

Author information

Affiliations

  1. Division of Pediatric Hematology/Oncology, Children’s Hospital Boston and Dana Farber Cancer Institute; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School; Division of Hematology, Brigham & Women’s Hospital, Boston, Massachusetts 02115, USA; and Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA

    • In-Hyun Park
    • , Rui Zhao
    • , Jason A. West
    • , Akiko Yabuuchi
    • , Hongguang Huo
    • , M. William Lensch
    •  & George Q. Daley
  2. Department of Pathology, Brigham and Women’s Hospital, and,

    • Tan A. Ince
  3. Division of Newborn Medicine, Brigham & Women’s Hospital and Children’s Hospital Boston, Boston, Massachusetts 02115, USA

    • Paul H. Lerou

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Corresponding author

Correspondence to George Q. Daley.

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    The file contains Supplementary Figures S1-S9 with Legends and Supplementary Table 1.

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https://doi.org/10.1038/nature06534

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