TY - JOUR
T1 - Runx1+ vascular smooth muscle cells are essential for hematopoietic stem and progenitor cell development in vivo
AU - Gonzalez Galofre, Zaniah N
AU - Kilpatrick, Alastair M
AU - Marques, Madalena
AU - Sá da Bandeira, Diana
AU - Ventura, Telma
AU - Gomez Salazar, Mario
AU - Bouilleau, Léa
AU - Marc, Yvan
AU - Barbosa, Ana B
AU - Rossi, Fiona
AU - Beltran, Mariana
AU - van de Werken, Harmen J G
AU - van IJcken, Wilfred F J
AU - Henderson, Neil C
AU - Forbes, Stuart J
AU - Crisan, Mihaela
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85185823547
U2 - 10.1038/s41467-024-44913-z
DO - 10.1038/s41467-024-44913-z
M3 - Article
C2 - 38395882
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1653
ER -