Article abstract


Nature Genetics 41, 968 - 976 (2009)
Published online: 9 August 2009 | doi:10.1038/ng.428

Differentiation stage determines potential of hematopoietic cells for reprogramming into induced pluripotent stem cells

Sarah Eminli1,2,3,4,8, Adlen Foudi1,3,8, Matthias Stadtfeld1,2,3, Nimet Maherali1,2,3,5, Tim Ahfeldt1,6, Gustavo Mostoslavsky7, Hanno Hock1,3 & Konrad Hochedlinger1,2,3


The reprogramming of somatic cells into induced pluripotent stem (iPS) cells upon overexpression of the transcription factors Oct4, Sox2, Klf4 and cMyc is inefficient. It has been assumed that the somatic differentiation state provides a barrier for efficient reprogramming; however, direct evidence for this notion is lacking. Here, we tested the potential of mouse hematopoietic cells at different stages of differentiation to be reprogrammed into iPS cells. We show that hematopoietic stem and progenitor cells give rise to iPS cells up to 300 times more efficiently than terminally differentiated B and T cells do, yielding reprogramming efficiencies of up to 28%. Our data provide evidence that the differentiation stage of the starting cell has a critical influence on the efficiency of reprogramming into iPS cells. Moreover, we identify hematopoietic progenitors as an attractive cell type for applications of iPS cell technology in research and therapy.

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  1. Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Boston, Massachusetts, USA.
  2. Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA.
  3. Harvard Stem Cell Institute, Cambridge, Massachusetts, USA.
  4. Free University of Berlin, Department of Biology, Chemistry and Pharmacy, Berlin, Germany.
  5. Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA.
  6. Department of Biochemistry and Molecular Biology II: Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  7. Section of Gastroenterology, Department of Medicine, Boston University School of Medicine and Center for Regenerative Medicine of Boston University, Boston, Massachusetts, USA.
  8. These authors contributed equally to this work.

Correspondence to: Konrad Hochedlinger1,2,3
e-mail: khochedlinger@helix.mgh.harvard.edu

Correspondence to: Hanno Hock1,3
e-mail: hock.hanno@mgh.harvard.edu



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