SDF-1 keeps HSC quiescent at home

Suggested models for the regulation of hematopoiesis by SDF-1. (A) A suggested model for the regulation of hematopoiesis and BM topography by SDF-1. (Left) In WT mice, hematopoiesis is localized mainly in close proximity to the endosteal and vascular regions, where LTR-HSCs self-renew and produce more committed progenitors. These progenitors proliferate and differentiate giving rise to all kinds of mature WBCs. (Right) In SDF-1-depleted mice, hematopoiesis is restricted to the vascular region, possibly due to endosteal niche dysfunction and/or due to increased levels of phosphorylated eNOS. SCF levels are down-regulated, and the LTR-HSC pool is decreased to the benefit of the enlarged progenitor pool. How the microenvironment (ME) itself is influenced by the lack of SDF-1 is yet to be defined. (B) A suggested model for the regulation of hematopoiesis by SDF-1 in steady state and after 5-FU myeloablation. (Left) During steady state, SDF-1-depleted mice have decreased levels of LTR-HSCs probably due to reduced self-renewal. In addition, these mice possess an enlarged proliferating pool of HSPCs with no change in WBC counts. (Right) After 5-FU myeloablation, SDF-1-depleted mice exhibit enhanced recovery of both progenitors and mature WBCs, probably also at the expense of LTR-HSCs. This enhanced hematopoietic recovery provides these mice with a clear survival advantage compared with WT mice. (Professional illustration by Paulette Dennis.)