CXCL12 is a chemokine required for maintenance of haematopoietic stem cells (HSCs) in mammals. HSCs reside in a specialized niche microenvironment in the bone marrow, but the identity of the niche cells providing the molecules required for HSC maintenance has been unclear. Ding and Morrison (Nature http://doi.org/krd; 2013) and Link and colleagues (Nature http://doi.org/krf; 2013) showed that HSCs depend on CXCL12 production in peristromal mesenchymal cells and in a subset of endothelial cells for their maintenance, whereas specific lymphoid progenitors rely on osteoblast-produced CXCL12.

Ding and Morrison used a mouse in which the fluorescent label ds-Red was knocked in at the endogenous CXCL12 locus. They found that it is expressed mainly in endothelial and perivascular stromal cells, and at lower levels in osteoblasts and haematopoietic cells; however, using a specific knockout, the authors ruled out that haematopoietic cells produce the CXCL12 maintains HSCs. An elegant series of cell-specific knockout experiments were performed by both groups. Deletion in endothelial cells led to loss of HSCs without an effect on myeloid or lymphoid progenitors, whereas deletion in osteoblasts depleted the lymphoid lineage. Deletion of CXCL12 from specific perivascular stromal cells induced a depletion of HSCs and some progenitors, and also mobilized the stem cells to the circulation. These data indicate the existence of distinct stem-cell- and progenitor-specific niches, and illustrate the complexity of niche–progenitor interactions in the bone marrow.