Stem cell factor acts locally in the bone marrow to promote stem and progenitor cell maintenance

Stem cell factor (SCF) from Leptin Receptor-expressing (LepR ⁺ ) mesenchymal stromal cells and endothelial cells is required for hematopoietic stem and progenitor cell maintenance in bone marrow. Consistent with this, Scf is highly expressed by LepR ⁺ cells and at lower levels by endothelial cells in bone marrow. However, endothelial cells outside the bone marrow produce circulating SCF, raising the question of whether the SCF that promotes stem and progenitor cell maintenance is produced inside or outside bone marrow. We found that Scf deletion in spleen and liver endothelial cells reduces SCF levels in the blood without affecting stem or progenitor numbers in the bone marrow. Moreover, deletion of Scf from mesenchymal cells in the long bones, but not vertebrae, of Prx1 ^Cre ; Scf ^fl/fl mice depletes stem and progenitor cells in long bones but not vertebrae. SCF thus acts locally within the bones in which it is made to promote stem and progenitor cell maintenance.

Scf deletion in endothelial cells outside of BM reduces SCF levels in blood without affecting stem or progenitor cell frequencies in BM Scf deletion from mesenchymal cells in long bones, but not vertebrae, depletes stem and progenitor cells in long bones but not vertebrae.