IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-48328-8.html
   My bibliography  Save this article

TFPI from erythroblasts drives heme production in central macrophages promoting erythropoiesis in polycythemia

Author

Listed:
  • Jun-Kai Ma

    (Zhejiang University School of Medicine)

  • Li-Da Su

    (Second Affiliated Hospital of Zhejiang University School of Medicine)

  • Lin-Lin Feng

    (Zhejiang University School of Medicine
    Ningbo University)

  • Jing-Lin Li

    (Zhejiang University School of Medicine)

  • Li Pan

    (The General Hospital of Tibet Military Area Command)

  • Qupei Danzeng

    (Department of Tibetan Medicine; University of Tibetan Medicine)

  • Yanwei Li

    (Zhejiang University School of Medicine)

  • Tongyao Shang

    (Zhejiang University School of Medicine)

  • Xiao-Lin Zhan

    (Zhejiang University School of Medicine
    Ningbo University)

  • Si-Ying Chen

    (Zhejiang University School of Medicine
    Ningbo University)

  • Shibo Ying

    (Hangzhou Medical College)

  • Jian-Rao Hu

    (Hangzhou Normal University)

  • Xue Qun Chen

    (School of Brain Science and Brain Medicine)

  • Qi Zhang

    (Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

  • Tingbo Liang

    (Zhejiang University School of Medicine
    Zhejiang University School of Medicine)

  • Xin-Jiang Lu

    (Zhejiang University School of Medicine)

Abstract

Bleeding and thrombosis are known as common complications of polycythemia for a long time. However, the role of coagulation system in erythropoiesis is unclear. Here, we discover that an anticoagulant protein tissue factor pathway inhibitor (TFPI) plays an essential role in erythropoiesis via the control of heme biosynthesis in central macrophages. TFPI levels are elevated in erythroblasts of human erythroblastic islands with JAK2V617F mutation and hypoxia condition. Erythroid lineage-specific knockout TFPI results in impaired erythropoiesis through decreasing ferrochelatase expression and heme biosynthesis in central macrophages. Mechanistically, the TFPI interacts with thrombomodulin to promote the downstream ERK1/2-GATA1 signaling pathway to induce heme biosynthesis in central macrophages. Furthermore, TFPI blockade impairs human erythropoiesis in vitro, and normalizes the erythroid compartment in mice with polycythemia. These results show that erythroblast-derived TFPI plays an important role in the regulation of erythropoiesis and reveal an interplay between erythroblasts and central macrophages.

Suggested Citation

  • Jun-Kai Ma & Li-Da Su & Lin-Lin Feng & Jing-Lin Li & Li Pan & Qupei Danzeng & Yanwei Li & Tongyao Shang & Xiao-Lin Zhan & Si-Ying Chen & Shibo Ying & Jian-Rao Hu & Xue Qun Chen & Qi Zhang & Tingbo Lia, 2024. "TFPI from erythroblasts drives heme production in central macrophages promoting erythropoiesis in polycythemia," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48328-8
    DOI: 10.1038/s41467-024-48328-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-48328-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-48328-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48328-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.