Oct4 and Klf4 Reprogram Dermal Papilla Cells into Induced Pluripotent Stem Cells§

Authors

  • Su-Yi Tsai,

    1. Black Family Stem Cell Institute,Mount Sinai School of Medicine, New York, New York, USA
    2. Department of Developmental and Regenerative Biology,Mount Sinai School of Medicine, New York, New York, USA
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  • Carlos Clavel,

    1. Black Family Stem Cell Institute,Mount Sinai School of Medicine, New York, New York, USA
    2. Department of Developmental and Regenerative Biology,Mount Sinai School of Medicine, New York, New York, USA
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  • Soo Kim,

    1. Black Family Stem Cell Institute,Mount Sinai School of Medicine, New York, New York, USA
    2. Department of Developmental and Regenerative Biology,Mount Sinai School of Medicine, New York, New York, USA
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  • Yen-Sin Ang,

    1. Black Family Stem Cell Institute,Mount Sinai School of Medicine, New York, New York, USA
    2. Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, New York, USA
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  • Laura Grisanti,

    1. Black Family Stem Cell Institute,Mount Sinai School of Medicine, New York, New York, USA
    2. Department of Developmental and Regenerative Biology,Mount Sinai School of Medicine, New York, New York, USA
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  • Dung-Fang Lee,

    1. Black Family Stem Cell Institute,Mount Sinai School of Medicine, New York, New York, USA
    2. Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, New York, USA
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  • Kevin Kelley,

    1. Black Family Stem Cell Institute,Mount Sinai School of Medicine, New York, New York, USA
    2. Department of Developmental and Regenerative Biology,Mount Sinai School of Medicine, New York, New York, USA
    3. Mouse Genetics Research Facility,Mount Sinai School of Medicine, New York, New York, USA
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  • Michael Rendl

    Corresponding author
    1. Black Family Stem Cell Institute,Mount Sinai School of Medicine, New York, New York, USA
    2. Department of Developmental and Regenerative Biology,Mount Sinai School of Medicine, New York, New York, USA
    3. Department of Dermatology, Mount Sinai School of Medicine, New York, New York, USA
    • Mount Sinai School of Medicine, Department of Developmental and Regenerative Biology, Black Family Stem Cell Institute, Atran Building, AB7-10C, Box 1020, 1428 Madison Avenue, New York, NY 10029, USA
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    • Telephone: 212-241-9593; Fax: 212-860-9279


  • Author contributions: S.Y.T.: conception and design, collection of data, data analysis and interpretation, manuscript writing; C.C., S.K.,Y.S.A., L.G., and D.F.L.: collection of data, data analysis and interpretation; C.C. and S.K. contributed equally to this work; K.K.: collection of data; M.R.: conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS January 28, 2010.

Abstract

Direct reprogramming of somatic cells into induced pluripotent stem (iPS) cells by only four transcription factors (Oct4, Sox2, Klf4, and c-Myc) has great potential for tissue-specific regenerative therapies, eliminating the ethical issues surrounding the use of embryonic stem cells and the rejection problems of using non-autologous cells. The reprogramming efficiency generally is very low, however, and the problems surrounding the introduction of viral genetic material are only partially investigated. Recent efforts to reduce the number of virally expressed transcription factors succeeded at reprogramming neural stem cells into iPS cells by overexpressing Oct4 alone. However, the relative inaccessibility and difficulty of obtaining neural cells in humans remains to be resolved. Here we report that dermal papilla (DP) cells, which are specialized skin fibroblasts thought to instruct hair follicle stem cells, endogenously express high levels of Sox2 and c-Myc, and that these cells can be reprogrammed into iPS cells with only Oct4 and Klf4. Moreover, we show that DP cells are reprogrammed more efficiently than skin and embryonic fibroblasts. iPS cells derived from DP cells expressed pluripotency genes and differentiated into cells from all germ layers in vitro and widely contributed to chimeric mice in vivo, including the germline. Our work establishes DP cells as an easily accessible source to generate iPS cells with efficiency and with less genetic material. This opens up the possibility of streamlined generation of skin-derived, patient-specific pluripotent stem cells and of ultimately replacing the remaining two factors with small molecules for safe generation of transplantable cells. STEM CELLS 2010;28:221–228

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