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Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming

Author

Listed:
  • Thomas Moreau

    (University of Cambridge and NHS Blood and Transplant
    The Anne McLaren Laboratory, University of Cambridge
    Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute)

  • Amanda L. Evans

    (University of Cambridge and NHS Blood and Transplant
    Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute)

  • Louella Vasquez

    (Human Genetics, Wellcome Trust Sanger Institute, Genome Campus)

  • Marloes R. Tijssen

    (University of Cambridge and NHS Blood and Transplant)

  • Ying Yan

    (Human Genetics, Wellcome Trust Sanger Institute, Genome Campus)

  • Matthew W. Trotter

    (The Anne McLaren Laboratory, University of Cambridge
    Present address: Celgene Institute for Translational Research Europe (CITRE), Parque Científico y Tecnológico Cartuja 93, Centro de Empresas Pabellón de Italia, Isaac Newton, 4, Seville E-41092, Spain.)

  • Daniel Howard

    (University of Cambridge and NHS Blood and Transplant
    Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute)

  • Maria Colzani

    (University of Cambridge and NHS Blood and Transplant
    Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute)

  • Meera Arumugam

    (University of Cambridge and NHS Blood and Transplant
    Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute)

  • Wing Han Wu

    (University of Cambridge and NHS Blood and Transplant
    Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute)

  • Amanda Dalby

    (University of Cambridge and NHS Blood and Transplant
    Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute)

  • Riina Lampela

    (Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute)

  • Guenaelle Bouet

    (University of Cambridge and NHS Blood and Transplant
    Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute)

  • Catherine M. Hobbs

    (University of Cambridge and NHS Blood and Transplant
    Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute)

  • Dean C. Pask

    (University of Cambridge and NHS Blood and Transplant
    Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute)

  • Holly Payne

    (Institute of Cardiovascular Sciences, University of Birmingham)

  • Tatyana Ponomaryov

    (Institute of Cardiovascular Sciences, University of Birmingham)

  • Alexander Brill

    (Institute of Cardiovascular Sciences, University of Birmingham)

  • Nicole Soranzo

    (Human Genetics, Wellcome Trust Sanger Institute, Genome Campus)

  • Willem H. Ouwehand

    (University of Cambridge and NHS Blood and Transplant)

  • Roger A. Pedersen

    (The Anne McLaren Laboratory, University of Cambridge
    Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute)

  • Cedric Ghevaert

    (University of Cambridge and NHS Blood and Transplant
    Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute)

Abstract

The production of megakaryocytes (MKs)—the precursors of blood platelets—from human pluripotent stem cells (hPSCs) offers exciting clinical opportunities for transfusion medicine. Here we describe an original approach for the large-scale generation of MKs in chemically defined conditions using a forward programming strategy relying on the concurrent exogenous expression of three transcription factors: GATA1, FLI1 and TAL1. The forward programmed MKs proliferate and differentiate in culture for several months with MK purity over 90% reaching up to 2 × 105 mature MKs per input hPSC. Functional platelets are generated throughout the culture allowing the prospective collection of several transfusion units from as few as 1 million starting hPSCs. The high cell purity and yield achieved by MK forward programming, combined with efficient cryopreservation and good manufacturing practice (GMP)-compatible culture, make this approach eminently suitable to both in vitro production of platelets for transfusion and basic research in MK and platelet biology.

Suggested Citation

  • Thomas Moreau & Amanda L. Evans & Louella Vasquez & Marloes R. Tijssen & Ying Yan & Matthew W. Trotter & Daniel Howard & Maria Colzani & Meera Arumugam & Wing Han Wu & Amanda Dalby & Riina Lampela & G, 2016. "Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming," Nature Communications, Nature, vol. 7(1), pages 1-16, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11208
    DOI: 10.1038/ncomms11208
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    Cited by:

    1. Mírian Romitti & Adrien Tourneur & Barbara Faria da Fonseca & Gilles Doumont & Pierre Gillotay & Xiao-Hui Liao & Sema Elif Eski & Gaetan Simaeys & Laura Chomette & Helene Lasolle & Olivier Monestier &, 2022. "Transplantable human thyroid organoids generated from embryonic stem cells to rescue hypothyroidism," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Parsa Akbari & Dragana Vuckovic & Luca Stefanucci & Tao Jiang & Kousik Kundu & Roman Kreuzhuber & Erik L. Bao & Janine H. Collins & Kate Downes & Luigi Grassi & Jose A. Guerrero & Stephen Kaptoge & Ju, 2023. "A genome-wide association study of blood cell morphology identifies cellular proteins implicated in disease aetiology," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Kai Kammers & Margaret A Taub & Ingo Ruczinski & Joshua Martin & Lisa R Yanek & Alyssa Frazee & Yongxing Gao & Dixie Hoyle & Nauder Faraday & Diane M Becker & Linzhao Cheng & Zack Z Wang & Jeff T Leek, 2017. "Integrity of Induced Pluripotent Stem Cell (iPSC) Derived Megakaryocytes as Assessed by Genetic and Transcriptomic Analysis," PLOS ONE, Public Library of Science, vol. 12(1), pages 1-16, January.

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