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 CD45' Ter119' CD31 ' CD166' CD146' Sca1 + (Sca1 +) progenitors give rise to CD45' Ter119' CD31 ' CD166' CD146 + (CD146 +) intermediate and CD45' Ter119' CD31 ' CD166 + CD146' (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.