Normal development of the bone marrow HSC niche (left) fails in the absence of Bmi1 (right).

Like baby chicks, stem cells need a nest—a niche within the body where they reside and self-renew. Oguro et al. (page 2247) find that, for blood stem cells, this nest is built by the same gene silencer that also helps them self-renew.

This silencer is Bmi1, which turns off two cell cycle inhibitor genes, Ink4a and Arf, to promote the self-renewal of hematopoietic stem cells (HSCs). Oguro et al. showed that defective HSC self-renewal in Bmi1-deficient mice can be restored by deletion of these cell cycle regulators, as previously observed in neural stem cells. But the new results show that HSC levels gradually decline as these mice age.

The authors wondered whether the progressive HSC problem might be due to defects in the HSC niche—the bone marrow microenvironment. Indeed, they found that development of the spongy meshwork structure of bone marrow in mice lacking Bmi1 was severely impaired and failed to support renewal of wild-type HSCs. The defects suggested that Bmi1 might be required for normal growth of the niche cells. The group showed that the proliferation of bone-forming osteoblasts was impaired in the absence of Bmi1. These findings fit well with previous reports that osteoblasts are important components of the HSC niche.

The defective niche was not rescued by deletion of Ink4a and Arf. Nest building in the bone marrow is therefore likely to require silencing of other Bmi1 targets. The team is currently searching for what those targets might be.