Single Transcription Factor Reprogramming of Hair Follicle Dermal Papilla Cells to Induced Pluripotent Stem Cells§

Authors

  • Su-Yi Tsai,

    1. Black Family Stem Cell InstituteMount Sinai School of Medicine, New York, New York, USA
    2. Department of Developmental and Regenerative BiologyMount Sinai School of Medicine, New York, New York, USA
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  • Britta Am Bouwman,

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

    1. Black Family Stem Cell InstituteMount Sinai School of Medicine, New York, New York, USA
    2. Department of Gene and Cell MedicineMount Sinai School of Medicine, New York, New York, USA
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  • Soo Jeong Kim,

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

    1. Black Family Stem Cell InstituteMount Sinai School of Medicine, New York, New York, USA
    2. Department of Gene and Cell MedicineMount Sinai School of Medicine, New York, New York, USA
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  • Ihor R. Lemischka,

    1. Black Family Stem Cell InstituteMount Sinai School of Medicine, New York, New York, USA
    2. Department of Gene and Cell MedicineMount Sinai School of Medicine, New York, New York, USA
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  • Michael Rendl

    Corresponding author
    1. Black Family Stem Cell InstituteMount Sinai School of Medicine, New York, New York, USA
    2. Department of Developmental and Regenerative BiologyMount Sinai School of Medicine, New York, New York, USA
    3. Department of Dermatology, Mount Sinai School of Medicine, New York, New York, USA
    • Black Family Stem Cell Institute, Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, Atran Building AB7-10C, Box 1020, 1428 Madison Avenue, New York, New York 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; B.B., Y.-S.A., S.J.K., and D.-F.L.: collection of data, data analysis and interpretation; I.L.: data analysis and interpretation; 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 April 19, 2011

Abstract

Reprogramming patient-specific somatic cells into induced pluripotent stem (iPS) cells has great potential to develop feasible regenerative therapies. However, several issues need to be resolved such as ease, efficiency, and safety of generation of iPS cells. Many different cell types have been reprogrammed, most conveniently even peripheral blood mononuclear cells. However, they typically require the enforced expression of several transcription factors, posing mutagenesis risks as exogenous genetic material. To reduce this risk, iPS cells were previously generated with Oct4 alone from rather inaccessible neural stem cells that endogenously express the remaining reprogramming factors and very recently from fibroblasts with Oct4 alone in combination with additional small molecules. Here, we exploit that dermal papilla (DP) cells from hair follicles in the skin express all but one reprogramming factors to show that these accessible cells can be reprogrammed into iPS cells with the single transcription factor Oct4 and without further manipulation. Reprogramming was already achieved after 3 weeks and with efficiencies similar to other cell types reprogrammed with four factors. Dermal papilla-derived iPS cells are comparable to embryonic stem cells with respect to morphology, gene expression, and pluripotency. We conclude that DP cells may represent a preferred cell type for reprogramming accessible cells with less manipulation and for ultimately establishing safe conditions in the future by replacing Oct4 with small molecules. STEM CELLS 2011;29:964–971

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