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Direct induction of haematoendothelial programs in human pluripotent stem cells by transcriptional regulators

Author

Listed:
  • Irina Elcheva

    (National Primate Research Center, University of Wisconsin Graduate School)

  • Vera Brok-Volchanskaya

    (National Primate Research Center, University of Wisconsin Graduate School)

  • Akhilesh Kumar

    (National Primate Research Center, University of Wisconsin Graduate School)

  • Patricia Liu

    (National Primate Research Center, University of Wisconsin Graduate School)

  • Jeong-Hee Lee

    (National Primate Research Center, University of Wisconsin Graduate School)

  • Lilian Tong

    (National Primate Research Center, University of Wisconsin Graduate School)

  • Maxim Vodyanik

    (National Primate Research Center, University of Wisconsin Graduate School)

  • Scott Swanson

    (Morgridge Institute for Research)

  • Ron Stewart

    (Morgridge Institute for Research)

  • Michael Kyba

    (Lillehei Heart Institute, University of Minnesota)

  • Eduard Yakubov

    (Center for Cardiovascular Regeneration, Houston Methodist Research Institute)

  • John Cooke

    (Center for Cardiovascular Regeneration, Houston Methodist Research Institute)

  • James A. Thomson

    (Morgridge Institute for Research
    University of Wisconsin School of Medicine and Public Health
    Cellular, and Developmental Biology, University of California)

  • Igor Slukvin

    (National Primate Research Center, University of Wisconsin Graduate School
    University of Wisconsin School of Medicine and Public Health
    University of Wisconsin Medical School)

Abstract

Advancing pluripotent stem cell technologies for modelling haematopoietic stem cell development and blood therapies requires identifying key regulators of haematopoietic commitment from human pluripotent stem cells (hPSCs). Here, by screening the effect of 27 candidate factors, we reveal two groups of transcriptional regulators capable of inducing distinct haematopoietic programs from hPSCs: pan-myeloid (ETV2 and GATA2) and erythro-megakaryocytic (GATA2 and TAL1). In both cases, these transcription factors directly convert hPSCs to endothelium, which subsequently transform into blood cells with pan-myeloid or erythro-megakaryocytic potential. These data demonstrate that two distinct genetic programs regulate the haematopoietic development from hPSCs and that both of these programs specify hPSCs directly to haemogenic endothelial cells. In addition, this study provides a novel method for the efficient induction of blood and endothelial cells from hPSCs via the overexpression of modified mRNA for the selected transcription factors.

Suggested Citation

  • Irina Elcheva & Vera Brok-Volchanskaya & Akhilesh Kumar & Patricia Liu & Jeong-Hee Lee & Lilian Tong & Maxim Vodyanik & Scott Swanson & Ron Stewart & Michael Kyba & Eduard Yakubov & John Cooke & James, 2014. "Direct induction of haematoendothelial programs in human pluripotent stem cells by transcriptional regulators," Nature Communications, Nature, vol. 5(1), pages 1-11, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5372
    DOI: 10.1038/ncomms5372
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