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

Nature communications 2024 Feb 23

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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. © 2024. The Author(s).

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 Beltran, Harmen J G van de Werken, Wilfred F J van IJcken, Neil C Henderson, Stuart J Forbes, Mihaela Crisan. Runx1+ vascular smooth muscle cells are essential for hematopoietic stem and progenitor cell development in vivo. Nature communications. 2024 Feb 23;15(1):1653