Figure 3. HSCs and restricted haematopoietic progenitors occupy distinct niches in the bone marrow

a. HSCs are found mainly adjacent to sinusoids throughout the bone marrow,,,, where endothelial cells and mesenchymal stromal cells promote HSC maintenance by producing SCF, CXCL12,,, and likely other factors. Similar cells may also promote HSC maintenance around other types of blood vessels, such as arterioles. The mesenchymal stromal cells can be identified based on their expression of Lepr-Cre, Prx1-Cre, Cxcl12-GFP, or Nestin-GFP transgene in mice and similar cells are likely to be identified by CD146 expression in humans. These perivascular stromal cells, which likely include Cxcl12-abundant Reticular (CAR) cells, are fated to form bone in vivo, express Mx-1-Cre and overlap with CD45/Ter119PDGFR +Sca-1+ stromal cells that are highly enriched for MSCs in culture. b. It is likely that other cells also contribute to this niche, likely including cells near bone surfaces in trabecular rich areas. Other cell types that regulate HSC niches include sympathetic nerves,, non-myelinating Schwann cells (which are also Nestin+), macrophages, osteoclasts, extracellular matrix ,, and calcium. Osteoblasts do not directly promote HSC maintenance but do promote the maintenance and perhaps the differentiation of certain lymphoid progenitors by secreting Cxcl12 and likely other factors,,,. Early lineage committed progenitors thus reside in an endosteal niche that is spatially and cellularly distinct from HSCs.

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The bone marrow niche for haematopoietic stem cells - PubMed