This niche is a maze; an amazing niche

Abstract

The cellular identity of niche cells that regulate hematopoietic stem cell (HSC) self-renewal and differentiation has been debated for several years. Two recent studies in Nature (Ding and Morrison, 2013; Greenbaum et al., 2013) have shed light into the bone marrow stromal subsets making CXCL12, a chemokine critical for HSC maintenance.

Figure 1. Distinct cellular sources and niches for CXCL12 in bone marrow

Most CXCL12 is derived from perivascular stromal cells that can be marked by Prx1-cre, Lepr-cre or Nestin-Gfp that likely show significant overlap with each other. The highest levels of CXCL12 is secreted by the most immature mesenchymal stem / progenitor cells. Osteoblasts, marked by Osteocalcin (Oc), synthesize low amounts of CXCL12 that are not essential for normal hematopoiesis, whereas deletion of Cxcl12 in osteoblasts using Col2.3-cre leads to deficits in certain early lymphoid progenitors similar to Osterix-cre, suggesting a contribution of osteoprogenitors in the generation of lymphoid precursors. Endothelial cells, marked by Tie2-cre, also secrete CXCL12 and contribute to HSC maintenance. Although some hematopoietic cells express CXCL12, deletion in the hematopoietic system using Vav1-cre did not yield any phenotype. The effect of Prx1-targeted cells on lymphoid progenitors is indicated with a dashed line since it is likely to be derived from osteoprogenitors or perivascular stromal Prx1-cre-targeted cell fraction. The size of circles does not reflect the actual frequencies in the bone marrow and the overlap among different models is based on estimations. HSC, hematopoietic stem cell; HPC, hematopoietic progenitor cell; CLP, common lymphoid progenitor; LMMP, lymphoid-primed multipotent progenitor.