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

Abstract

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.