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Murine hematopoietic progenitor cell lines with erythroid and megakaryocyte potential

Author

Listed:
  • Ruiqiong Wu

    (St. Jude Children’s Research Hospital)

  • Faraz Salehi

    (University of Utah School of Medicine)

  • Vanessa Redecke

    (University of Utah School of Medicine)

  • Zhijun Ma

    (St. Jude Children’s Research Hospital)

  • Marco Marchetti

    (University of Utah)

  • David Finkelstein

    (St. Jude Children’s Research Hospital)

  • Peng Xu

    (St. Jude Children’s Research Hospital
    Soochow University)

  • Yong Cheng

    (St. Jude Children’s Research Hospital)

  • Kimberly A. Queisser

    (University of Utah School of Medicine)

  • Aaron C. Petrey

    (University of Utah School of Medicine)

  • Conroy O. Field

    (Children’s Hospital of Philadelphia)

  • Hyun Sook Ahn

    (Children’s Hospital of Philadelphia)

  • Mortimer Poncz

    (Children’s Hospital of Philadelphia)

  • Mitchell J. Weiss

    (St. Jude Children’s Research Hospital)

  • Hans Häcker

    (University of Utah School of Medicine)

Abstract

Red blood cells and platelets derive from bi-potential bone marrow megakaryocyte-erythroid progenitors, but their study is constrained by cell scarcity and limited experimental systems. Here we show that conditional expression of a virally transduced, regulated form of Hoxa7 enables expansion of murine cells resembling megakaryocyte-erythroid progenitors (Hoxa7-TPO), which undergo erythro-megakaryocytic differentiation upon Hoxa7 inactivation. The close relationship of Hoxa7-TPO cells to megakaryocyte-erythroid progenitors is supported by genetic and phenotypic analyses, and mature Hoxa7-TPO-derived red blood cells and platelets are largely indistinguishable from their primary counterparts. Genetic knock-out studies in Hoxa7-TPO cells recapitulate the key function of Klf1 and Nfe2 in red blood cell and platelet development, respectively, while disruption of the von Willebrand receptor gene Gp1ba recapitulates features of human Bernard-Soulier syndrome. Hence, we developed a versatile experimental system for expansion and differentiation of megakaryocyte-erythroid progenitors to study red blood cell and platelet development and model human diseases.

Suggested Citation

  • Ruiqiong Wu & Faraz Salehi & Vanessa Redecke & Zhijun Ma & Marco Marchetti & David Finkelstein & Peng Xu & Yong Cheng & Kimberly A. Queisser & Aaron C. Petrey & Conroy O. Field & Hyun Sook Ahn & Morti, 2025. "Murine hematopoietic progenitor cell lines with erythroid and megakaryocyte potential," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62668-z
    DOI: 10.1038/s41467-025-62668-z
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    References listed on IDEAS

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    1. Kongtana Trakarnsanga & Rebecca E. Griffiths & Marieangela C. Wilson & Allison Blair & Timothy J. Satchwell & Marjolein Meinders & Nicola Cogan & Sabine Kupzig & Ryo Kurita & Yukio Nakamura & Ashley M, 2017. "An immortalized adult human erythroid line facilitates sustainable and scalable generation of functional red cells," Nature Communications, Nature, vol. 8(1), pages 1-7, April.
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