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Runx1+ vascular smooth muscle cells are essential for hematopoietic stem and progenitor cell development in vivo

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  • Zaniah N. Gonzalez Galofre

    (The University of Edinburgh
    The University of Edinburgh)

  • Alastair M. Kilpatrick

    (The University of Edinburgh)

  • Madalena Marques

    (The University of Edinburgh)

  • Diana Sá da Bandeira

    (The University of Edinburgh
    The University of Edinburgh)

  • Telma Ventura

    (The University of Edinburgh)

  • Mario Gomez Salazar

    (The University of Edinburgh)

  • Léa Bouilleau

    (The University of Edinburgh)

  • Yvan Marc

    (The University of Edinburgh)

  • Ana B. Barbosa

    (The University of Edinburgh)

  • Fiona Rossi

    (The University of Edinburgh)

  • Mariana Beltran

    (The University of Edinburgh)

  • Harmen J. G. Werken

    (Erasmus MC Cancer Institute, University Medical Center
    Erasmus MC Cancer Institute, University Medical Center
    Erasmus MC Cancer Institute, University Medical Center)

  • Wilfred F. J. IJcken

    (Erasmus MC University Medical Centre)

  • Neil C. Henderson

    (The University of Edinburgh
    The University of Edinburgh)

  • Stuart J. Forbes

    (The University of Edinburgh)

  • Mihaela Crisan

    (The University of Edinburgh
    The University of Edinburgh)

Abstract

Hematopoietic stem cells (HSCs) produce all essential cellular components of the blood. Stromal cell lines supporting HSCs follow a vascular smooth muscle cell (vSMC) differentiation pathway, suggesting that some hematopoiesis-supporting cells originate from vSMC precursors. These pericyte-like precursors were recently identified in the aorta-gonad-mesonephros (AGM) region; however, their role in the hematopoietic development in vivo remains unknown. Here, we identify a subpopulation of NG2+Runx1+ perivascular cells that display a sclerotome-derived vSMC transcriptomic profile. We show that deleting Runx1 in NG2+ cells impairs the hematopoietic development in vivo and causes transcriptional changes in pericytes/vSMCs, endothelial cells and hematopoietic cells in the murine AGM. Importantly, this deletion leads also to a significant reduction of HSC reconstitution potential in the bone marrow in vivo. This defect is developmental, as NG2+Runx1+ cells were not detected in the adult bone marrow, demonstrating the existence of a specialised pericyte population in the HSC-generating niche, unique to the embryo.

Suggested Citation

  • Zaniah N. Gonzalez Galofre & Alastair M. Kilpatrick & Madalena Marques & Diana Sá da Bandeira & Telma Ventura & Mario Gomez Salazar & Léa Bouilleau & Yvan Marc & Ana B. Barbosa & Fiona Rossi & Mariana, 2024. "Runx1+ vascular smooth muscle cells are essential for hematopoietic stem and progenitor cell development in vivo," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44913-z
    DOI: 10.1038/s41467-024-44913-z
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