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.