Scientific article
English

Arteriolar niches maintain haematopoietic stem cell quiescence

Published inNature, vol. 502, no. 7473, p. 637-643
Publication date2013
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 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.

Keywords
  • Animals
  • Arterioles/cytology
  • Bone Marrow/blood supply
  • Cell Division
  • Cell Separation
  • Female
  • Flow Cytometry
  • Hematopoietic Stem Cells/cytology/metabolism
  • Male
  • Mesenchymal Stromal Cells/cytology
  • Mice
  • Mice, Inbred C57BL
  • Nestin/metabolism
  • Stem Cell Niche
Affiliation entities Not a UNIGE publication
Citation (ISO format)
KUNISAKI, Yuya et al. Arteriolar niches maintain haematopoietic stem cell quiescence. In: Nature, 2013, vol. 502, n° 7473, p. 637–643. doi: 10.1038/nature12612
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Article (Published version)
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Identifiers
Journal ISSN0028-0836
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