Reprogramming of human somatic cells to pluripotency with defined factors

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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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 the OCT4 and NANOG 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 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).

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Correspondence to George Q. Daley.

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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. Nature 451, 141–146 (2008). https://doi.org/10.1038/nature06534

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