Hematopoietic and Endothelial Differentiation of Human Induced Pluripotent Stem Cells§

Authors

  • Kyung-Dal Choi,

    1. Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin, USA
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  • Junying Yu,

    1. Department of Genome Center of Wisconsin, University of Wisconsin, Madison, Wisconsin, USA
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  • Kim Smuga-Otto,

    1. Department of Wisconsin National Primate Research Center, University of Wisconsin, Madison, Wisconsin, USA
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  • Giorgia Salvagiotto,

    1. Department of WiCell Research Institute, University of Wisconsin, Madison, Wisconsin, USA
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  • William Rehrauer,

    1. Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin, USA
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  • Maxim Vodyanik,

    1. Department of Wisconsin National Primate Research Center, University of Wisconsin, Madison, Wisconsin, USA
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  • James Thomson,

    1. Department of Genome Center of Wisconsin, University of Wisconsin, Madison, Wisconsin, USA
    2. Department of Wisconsin National Primate Research Center, University of Wisconsin, Madison, Wisconsin, USA
    3. Department of Anatomy, University of Wisconsin, Madison, Wisconsin, USA
    4. Department of Morgridge Institute for Research, Madison, Wisconsin, USA
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  • Igor Slukvin

    Corresponding author
    1. Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin, USA
    2. Department of Genome Center of Wisconsin, University of Wisconsin, Madison, Wisconsin, USA
    3. Department of Wisconsin National Primate Research Center, University of Wisconsin, Madison, Wisconsin, USA
    • Department of Pathology and Laboratory Medicine, Wisconsin National Primate Research Center, University of Wisconsin, 1220 Capitol Court, Madison, Wisconsin 53715, USA
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    • Telephone: (608) 263 0058; Fax: (608) 265 8984


  • First published online in STEM CELLSExpress January 8, 2009.

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

  • §

    Author contributions: K.-D.C., G.S., and M.V.: collection and assembly of data, conception and design, data analysis; W.R.: collection of data; J.T.: conception, generation of iPSC lines; J.Y. and K.S.-O.: generation of iPSC lines; I.S.: conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript.

Abstract

Induced pluripotent stem cells (iPSCs) provide an unprecedented opportunity for modeling of human diseases in vitro, as well as for developing novel approaches for regenerative therapy based on immunologically compatible cells. In this study, we employed an OP9 differentiation system to characterize the hematopoietic and endothelial differentiation potential of seven human iPSC lines obtained from human fetal, neonatal, and adult fibroblasts through reprogramming with POU5F1, SOX2, NANOG, and LIN28 and compared it with the differentiation potential of five human embryonic stem cell lines (hESC, H1, H7, H9, H13, and H14). Similar to hESCs, all iPSCs generated CD34+CD43+ hematopoietic progenitors and CD31+CD43 endothelial cells in coculture with OP9. When cultured in semisolid media in the presence of hematopoietic growth factors, iPSC-derived primitive blood cells formed all types of hematopoietic colonies, including GEMM colony-forming cells. Human induced pluripotent cells (hiPSCs)-derived CD43+ cells could be separated into the following phenotypically defined subsets of primitive hematopoietic cells: CD43+CD235a+CD41a± (erythro-megakaryopoietic), linCD34+CD43+CD45 (multipotent), and linCD34+CD43+CD45+ (myeloid-skewed) cells. Although we observed some variations in the efficiency of hematopoietic differentiation between different hiPSCs, the pattern of differentiation was very similar in all seven tested lines obtained through reprogramming of human fetal, neonatal, or adult fibroblasts with three or four genes. Although several issues remain to be resolved before iPSC-derived blood cells can be administered to humans for therapeutic purposes, patient-specific iPSCs can already be used for characterization of mechanisms of blood diseases and for identification of molecules that can correct affected genetic networks. STEM CELLS2009;27:559–567

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