Identification of a common mesenchymal stromal progenitor for the adult haematopoietic niche.

Microenvironment cues received by haematopoietic stem cells (HSC) are important in regulating the choice between self-renewal and differentiation. On the basis of the differential expression of cell-surface markers, here we identify a mesenchymal stromal progenitor hierarchy, where CD45Ter119CD31CD166CD146Sca1(Sca1) progenitors give rise to CD45Ter119CD31CD166CD146(CD146) intermediate and CD45Ter119CD31CD166CD146(CD166) mature osteo-progenitors. All three progenitors preserve HSC long-term multi-lineage reconstitution capability in vitro; however, their in vivo fates are different. Post-transplantation, CD146 and CD166 progenitors form bone only. While Sca1 progenitors produce CD146, CD166 progenitors, osteocytes and CXCL12-producing stromal cells. Only Sca1 progenitors are capable of homing back to the marrow post-intravenous infusion. Ablation of Sca1 progenitors results in a decrease of all three progenitor populations as well as haematopoietic stem/progenitor cells. Moreover, suppressing production of KIT-ligand in Sca1 progenitors inhibits their ability to support HSCs. Our results indicate that Sca1 progenitors, through the generation of both osteogenic and stromal cells, provide a supportive environment for hematopoiesis.