Phenotypically identical hemopoietic stem cells isolated from different regions of bone marrow have different biologic potential

Hemopoietic stem cells (HSC) reside within a specified area of the bone marrow (BM) cavity called a niche that modulates HSC quiescence, proliferation, differentiation and migration. Our previous studies, have identified the endosteal BM region as the site for the HSC niche, and demonstrated that hemopoietic stem and progenitor populations (HSPC, LSK) isolated from different BM regions exhibit significantly different hemopoietic potential. In this study we have analyzed subpopulations of LSK cells isolated from different regions of the BM and showed that CD150(+)CD48(-)LSK HSC within the endosteal BM region have superior proliferative capacity and homing efficiency compared to CD150(+)CD48(-)LSK HSC isolated from the central BM. Furthermore we show for the first time that a subset of CD150(+)CD48(+)LSK progenitor cells, previously defined as B-lymphoid primed hemopoietic cells, are capable of multi-lineage reconstitution, however, only when isolated from the endosteal region. In addition, we provide evidence for an unrecognized role of CD48 in HSC homing. Together our data provides strong evidence that highly purified HSC show functional differences depending on their origin within the BM and that the most primitive HSC reside within the endosteal BM region.