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

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Abstract
Konrad Hochedlinger and colleagues show that hematopoietic stem and progenitor cells give rise to induced pluripotent stem cells 300 times more efficiently than terminally differentiated B and T lymphocytes, yielding reprogramming efficiencies of up to 27%. These findings identify adult hematopoietic progenitors as an attractive cell type for applications of iPS technology in research and therapy. 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.