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Ezh2 is essential for the generation of functional yolk sac derived erythro-myeloid progenitors

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  • Wen Hao Neo

    (University of Oxford
    The University of Manchester)

  • Yiran Meng

    (University of Oxford)

  • Alba Rodriguez-Meira

    (University of Oxford)

  • Muhammad Z. H. Fadlullah

    (The University of Manchester)

  • Christopher A. G. Booth

    (University of Oxford)

  • Emanuele Azzoni

    (University of Oxford
    University of Milano-Bicocca)

  • Supat Thongjuea

    (University of Oxford)

  • Marella F. T. R. Bruijn

    (University of Oxford)

  • Sten Eirik W. Jacobsen

    (University of Oxford
    Karolinska Institutet and Karolinska University Hospital)

  • Adam J. Mead

    (University of Oxford)

  • Georges Lacaud

    (The University of Manchester)

Abstract

Yolk sac (YS) hematopoiesis is critical for the survival of the embryo and a major source of tissue-resident macrophages that persist into adulthood. Yet, the transcriptional and epigenetic regulation of YS hematopoiesis remains poorly characterized. Here we report that the epigenetic regulator Ezh2 is essential for YS hematopoiesis but dispensable for subsequent aorta–gonad–mesonephros (AGM) blood development. Loss of EZH2 activity in hemogenic endothelium (HE) leads to the generation of phenotypically intact but functionally deficient erythro-myeloid progenitors (EMPs), while the generation of primitive erythroid cells is not affected. EZH2 activity is critical for the generation of functional EMPs at the onset of the endothelial-to-hematopoietic transition but subsequently dispensable. We identify a lack of Wnt signaling downregulation as the primary reason for the production of non-functional EMPs. Together, our findings demonstrate a critical and stage-specific role of Ezh2 in modulating Wnt signaling during the generation of EMPs from YS HE.

Suggested Citation

  • Wen Hao Neo & Yiran Meng & Alba Rodriguez-Meira & Muhammad Z. H. Fadlullah & Christopher A. G. Booth & Emanuele Azzoni & Supat Thongjuea & Marella F. T. R. Bruijn & Sten Eirik W. Jacobsen & Adam J. Me, 2021. "Ezh2 is essential for the generation of functional yolk sac derived erythro-myeloid progenitors," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27140-8
    DOI: 10.1038/s41467-021-27140-8
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