Model of osteoblast-mediated HSC mobilization and maintenance of reconstituting potential. (A) Osteoblasts (blue) within the normal BM microenvironment appear to negatively regulate HSC proliferation (red), at least in part through cell-cell contact. (B) Changes in the osteoblast compartment induced by Cy/G treatment (indicated by yellow star) alter the niche (red star) such that osteoblasts promote HSC proliferation and maintain HSC reconstitution potential. This alteration could arise in vivo directly, by regulation of fully differentiated osteoblasts by Cy/G, or indirectly, via (1) the stimulation/proliferation of more primitive osteoprogenitor cells (blue) or (2) the cross-regulation/activation of osteoblasts by osteoclasts (green) or other stromal elements (brown), that through an ATM dependent mechanism results in (3) a specialized subset of osteolineage cells that are sufficient to promote HSC self-renewal through the secretion of soluble factors (pink asterisks).