Arteriolar niches maintain haematopoietic stem cell quiescence

Abstract

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 (BM) remains unclear. Here, using a novel approach that combines whole-mount confocal immunofluorescence imaging techniques and computational modelling to analyse significant tridimensional associations among vascular structures, stromal cells and HSCs, we show that quiescent HSCs associate specifically with small arterioles that are preferentially found in endosteal BM. These arterioles are ensheathed exclusively by rare NG2 ⁺ pericytes, distinct from sinusoid-associated LepR ⁺ cells. Pharmacological or genetic activation of HSC cell cycle alters the distribution of HSCs from NG2 ⁺ peri-arteriolar niches to LepR ⁺ peri-sinusoidal niches. Conditional depletion of NG2 ⁺ cells induces HSC cycling and reduces functional long-term repopulating HSCs in BM. These results thus indicate that arteriolar niches are indispensable to maintain HSC quiescence.