BM endothelial cells are hierarchically organized, with a hemogenic transplantable stem cell at the apex, giving rise to functional blood vessels as well as the entire blood system.GCOE Program Seminar(Global Education Seminar)

Hemopoietic stem cells reside in marrow niches and are responsible for producing all circulating blood cells. Interfacing blood and the niche are sinusoidal endothelial cell lined vessels, with immense endocytic capacity. Bone marrow sinusoids have previously been identified as critical in stem cell regulation, comprising a key component of the niche. However, little is known about the characteristics or functional capacity of bone marrow endothelial cells. We have recently identified, prospectively isolated and characterized bone marrow scavenging endothelial cells (BMSEC), demonstrating a hierarchical organization and a subpopulation highly enriched for hemogenic endothelial stem cells with long-term serial transplant potential, revascularization of recipient marrow as well as giving rise to long-term multi-lineage reconstituting blood stem cells (HSC; LSK SLAM). Furthermore, these cells represent the adult hemangioblast, recapitulating the endothelial and hemopoietic systems following single cell transplantation. In addition, HSC themselves, were shown to be bi-potent and demonstrated hemangioblast potential at the single cell level post-transplant. Endothelial stem cells derived from HSC were also serially transplantable re-recapitulating the complete endothelial cell hierarchy. These findings represent a major advance in the understanding of HSC and marrow endothelial cells, and importantly the recognition of the ability of each population to give rise to the other in vivo. Identification of human counterparts of these endothelial cells and their use in transplantation may lead to improved clinical outcomes.(Language) (English)