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Publication : Arteriolar niches maintain haematopoietic stem cell quiescence.

First Author  Kunisaki Y Year  2013
Journal  Nature Volume  502
Issue  7473 Pages  637-43
PubMed ID  24107994 Mgi Jnum  J:274611
Mgi Id  MGI:6210330 Doi  10.1038/nature12612
Citation  Kunisaki Y, et al. (2013) Arteriolar niches maintain haematopoietic stem cell quiescence. Nature 502(7473):637-43
abstractText  Cell cycle quiescence is a critical feature contributing to haematopoietic stem cell (HSC) maintenance. Although various candidate stromal cells have been identified as potential HSC niches, the spatial localization of quiescent HSCs in the bone marrow remains unclear. Here, using a novel approach that combines whole-mount confocal immunofluorescence imaging techniques and computational modelling to analyse significant three-dimensional associations in the mouse bone marrow among vascular structures, stromal cells and HSCs, we show that quiescent HSCs associate specifically with small arterioles that are preferentially found in endosteal bone marrow. These arterioles are ensheathed exclusively by rare NG2 (also known as CSPG4)(+) pericytes, distinct from sinusoid-associated leptin receptor (LEPR)(+) cells. Pharmacological or genetic activation of the HSC cell cycle alters the distribution of HSCs from NG2(+) periarteriolar niches to LEPR(+) perisinusoidal niches. Conditional depletion of NG2(+) cells induces HSC cycling and reduces functional long-term repopulating HSCs in the bone marrow. These results thus indicate that arteriolar niches are indispensable for maintaining HSC quiescence.
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