Runx1+ vascular smooth muscle cells are essential for hematopoietic stem and progenitor cell development in vivo.
Zaniah N Gonzalez GalofreAlastair M KilpatrickMadalena MarquesDiana Sa da BandeiraTelma VenturaMario Gomez SalazarLéa BouilleauYvan MarcAna B BarbosaFiona RossiMariana BeltranHarmen J G van de WerkenWilfred F J Van IJckenNeil Cowan HendersonStuart John ForbesMihaela CrisanPublished in: Nature communications (2024)
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.
Keyphrases
- induced apoptosis
- bone marrow
- cell cycle arrest
- endothelial cells
- vascular smooth muscle cells
- endoplasmic reticulum stress
- smooth muscle
- pregnant women
- blood brain barrier
- oxidative stress
- stem cells
- coronary artery
- angiotensin ii
- aortic valve
- cell therapy
- climate change
- rna seq
- pulmonary artery
- heat shock protein
- human health