Hematopoietic Development from Human Induced Pluripotent Stem Cells

Authors

  • Claudia Lengerke,

    1. Division of Hematology and Oncology, University of Tuebingen Medical Center II, Tuebingen, Germany
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  • Matthias Grauer,

    1. Division of Hematology and Oncology, University of Tuebingen Medical Center II, Tuebingen, Germany
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  • Nina I. Niebuhr,

    1. Division of Hematology and Oncology, University of Tuebingen Medical Center II, Tuebingen, Germany
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  • Tamara Riedt,

    1. Division of Hematology and Oncology, University of Tuebingen Medical Center II, Tuebingen, Germany
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  • Lothar Kanz,

    1. Division of Hematology and Oncology, University of Tuebingen Medical Center II, Tuebingen, Germany
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  • In-Hyun Park,

    1. Howard Hughes Medical Institute, USA
    2. Division of Hematology/Oncology, Children's Hospital Boston, Boston, Massachusetts, USA
    3. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA
    4. Harvard Stem Cell Institute, Cambridge, Massachusetts, USA
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  • George Q. Daley

    1. Howard Hughes Medical Institute, USA
    2. Division of Hematology/Oncology, Children's Hospital Boston, Boston, Massachusetts, USA
    3. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA
    4. Harvard Stem Cell Institute, Cambridge, Massachusetts, USA
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Address for correspondence: Claudia Lengerke, M.D., Division of Hematology and Oncology, University of Tuebingen Medical Center II, Otfried-Mueller-Str. 10, 72074 Tuebingen, Germany. Voice: +49-7071-2982912; fax: +49-7071-294524. claudia.lengerke@med.uni-tuebingen.de

Abstract

A decade of research on human embryonic stem cells (ESC) has paved the way for the discovery of alternative approaches to generating pluripotent stem cells. Combinatorial overexpression of a limited number of proteins linked to pluripotency in ESC was recently found to reprogram differentiated somatic cells back to a pluripotent state, enabling the derivation of isogenic (patient-specific) pluripotent stem cell lines. Current research is focusing on improving reprogramming protocols (e.g., circumventing the use of retroviral technology and oncoproteins), and on methods for differentiation into transplantable tissues of interest. In mouse ESC, we have previously shown that the embryonic morphogens BMP4 and Wnt3a direct blood formation via activation of Cdx and Hox genes. Ectopic expression of Cdx4 and HoxB4 enables the generation of mouse ESC-derived hematopoietic stem cells (HSC) capable of multilineage reconstitution of lethally irradiated adult mice. Here, we explore hematopoietic development from human induced pluripotent stem (iPS) cells generated in our laboratory. Our data show robust differentiation of iPS cells to mesoderm and to blood lineages, as shown by generation of CD34+CD45+ cells, hematopoietic colony activity, and gene expression data, and suggest conservation of blood patterning pathways between mouse and human hematopoietic development.

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