Runx1+ vascular smooth muscle cells are essential for hematopoietic stem and progenitor cell development in vivo
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 Beltran,
Harmen J. G. Werken,
Wilfred F. J. IJcken,
Neil C. Henderson,
Stuart J. Forbes and
Mihaela Crisan ()
Additional contact information
Zaniah N. Gonzalez Galofre: 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
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
Wilfred F. J. IJcken: Erasmus MC University Medical Centre
Neil C. Henderson: The University of Edinburgh
Stuart J. Forbes: The University of Edinburgh
Mihaela Crisan: The University of Edinburgh
Nature Communications, 2024, vol. 15, issue 1, 1-17
Abstract:
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.
Date: 2024
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44913-z
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DOI: 10.1038/s41467-024-44913-z
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