Runx1+ vascular smooth muscle cells are essential for hematopoietic stem and progenitor cell development in vivo
Zaniah González, Alastair M. Kilpatrick, Madalena Marques, Diana Sá da Bandeira, Telma Ventura, Mario Gomez-Salazar, lea Bouilleau, Yvan Marc, Ana B. Barbosa, Fiona Rossi, Mariana Beltrán, Harmen J.G. van de Werken, Wilfred F. J. van IJcken, Neil C. Henderson, Stuart J. Forbes, Mihaela Crisan
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.