Adult haematopoietic stem cell niches

Dividing and non-dividing haematopoietic stem cells (HSCs) reside in perivascular niches that are mainly associated with sinusoidal blood vessels in adult bone marrow and spleen.A subset of HSCs is most closely associated with arterioles. The periarteriolar and perisinusoidal microenvironments differ in terms of the capacity of HSCs to intravasate into the circulation and in terms of their exposure to blood plasma components.Endothelial cells and leptin receptor-expressing, CXC-chemokine ligand 12 (CXCL12)-abundant reticular perivascular stromal cells are the main sources of the stem cell factor (SCF) and CXCL12 required for HSC maintenance in normal young-adult bone marrow. Other perivascular cells, such as Ng2-CreER+ periarteriolar cells (which express neural–glial antigen 2), may or may not also synthesize the CXCL12 required for HSC maintenance.Several other cell types — including megakaryocytes, monocytes and macrophages, neurons (specifically, nerve fibres) and Schwann cells — directly or indirectly regulate HSC or niche function through other mechanisms.Extramedullary haematopoiesis in the spleen depends on a perivascular niche that is associated with sinusoids in the red pulp, in which endothelial cells and transcription factor 21-expressing stromal cells are the main sources of SCF and CXCL12. This niche is necessary for the recovery of haematopoiesis from haematopoietic stresses such as blood loss.The vascular and stromal compositions of the bone marrow change during ageing.