Myelosuppression damages the bone Seven Histone Methyltransferase Techniques Explained marrow (BM) vascular niche, but it is unclear how regeneration of bone marrow vessels contributes to engraftment of transplanted hematopoietic stem and progenitor Seven Histone Methyltransferase Procedures Defined cells (HSPCs) and restoration of hematopoiesis. We found that chemotherapy and sublethal irradiation induced minor regression of BM sinusoidal endothelial cells (SECs), when lethal irradiation induced significant regression of SECs and required BM transplantation (BMT) for regeneration. Inside the BM, VEGFR2 expression exclusively demarcated a constant network of arterioles and SECs, with arterioles uniquely expressing Sca1 and SECs uniquely expressing VEGFR3. Conditional deletion of VEGFR2 in adult mice blocked regeneration of SECs in sublethally irradiated animals and prevented hematopoietic reconstitution. Similarly, inhibition of VEGFR2 signaling in lethally irradiated wild-type mice rescued with BMT severely impaired SEC reconstruction and prevented engraftment and reconstitution of HSPCs. Therefore, regeneration of SECs via VEGFR2 signaling is vital for engraftment of HSPCs and Ten Histone Methyltransferase Techniques Outlined restoration of hematopoiesis.