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Reprogramming of human somatic cells to pluripotency with defined factors

Naturevolume 451, pages141–146 (2008)Cite this article

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 andMyc) 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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Figure 1:Differentiation of human embryonic fibroblasts from human embryonic stem cells (H1-OGN).
Figure 2:Multiple cultured human primary somatic cells yield iPS cells.
Figure 3:Gene expression in human iPS cells is similar to human ES cells.
Figure 4:iPS cells are demethylated at theOCT4 andNANOG promoters relative to their fibroblast parent lines.
Figure 5:Global gene expression analysis of iPS cells.
Figure 6:Xenografts of human iPS cells generate well-differentiated teratoma-like masses containing all three embryonic germ layers.

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Gene Expression Omnibus

Data deposits

The microarray data have been deposited in GEO and given the series accession numberGSE9832.

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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).

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Authors and Affiliations

  1. Division of Pediatric Hematology/Oncology, Children’s Hospital Boston and Dana Farber Cancer Institute; 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 Biological Chemistry and Molecular Pharmacology, Harvard Medical School,

    In-Hyun Park, Rui Zhao, Jason A. West, Akiko Yabuuchi, Hongguang Huo, M. William Lensch & George Q. Daley

  3. Department of Pathology, Brigham and Women’s Hospital, and,

    Tan A. Ince

  4. Division of Newborn Medicine, Brigham & Women’s Hospital and Children’s Hospital Boston, Boston, Massachusetts 02115, USA,

    Paul H. Lerou

Authors
  1. In-Hyun Park

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  2. Rui Zhao

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  3. Jason A. West

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  4. Akiko Yabuuchi

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  5. Hongguang Huo

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  6. Tan A. Ince

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  7. Paul H. Lerou

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  8. M. William Lensch

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  9. George Q. Daley

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Corresponding author

Correspondence toGeorge Q. Daley.

Supplementary information

Supplementary Information

The file contains Supplementary Figures S1-S9 with Legends and Supplementary Table 1. (PDF 4983 kb)

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Park, IH., Zhao, R., West, J.et al. Reprogramming of human somatic cells to pluripotency with defined factors.Nature451, 141–146 (2008). https://doi.org/10.1038/nature06534

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Editorial Summary

Stem cells get personal

Another important step in the rapidly developing world of human stem cells is reported in this issue. Human cells taken from adult donors have been reprogrammed to produce iPS (induced pluripotent stem) cells, resembling embryonic stem cells in their main characteristics. It may soon be possible to use such procedures routinely to isolate patient-specific cells in culture.

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