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Characterizing the extracellular components of the hemopoietic stem cell niche
Author(s) -
Nilsson Susie
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.387.2
Subject(s) - haematopoiesis , stem cell , microbiology and biotechnology , niche , biology , hematopoietic stem cell , bone marrow , immunology , biochemistry
Considerable evidence supports the proposal that hemopoietic localisation to marrow involves developmentally regulated adhesive interactions between hemopoietic stem cells (HSC) and the microenvironment. Our previous studies demonstrate that HSC reside within an endosteal stem cell niche, and identified several molecules that play critical roles in their attraction to, and retention and regulation within this region. We have described Hyaluronic acid (HA) as one of these molecules and shown that human and murine HSC synthesise and express HA. We demonstrated that HA is critical in the trans‐marrow migration, lodgement and regulation of HSC in their niche. Analysis of HAS−/− mice identify HA synthase 3 (HAS 3) as the main synthase mediating this component of HSC engraftment. In the absence of HAS‐3 synthase the endosteal region is devoid of HA, and the microenvironment is significantly impaired in its ability to attract and support HSC post‐transplant as well as regulate the HSC pool in vivo. Furthermore, transplanted HSC isolated from HAS‐3−/− mice have a reduced ability to lodge within the endosteal region and reconstitute hemopoiesis. In vitro, HA binding by a surrogate ligand has a negative regulatory effect of HSC proliferation and differentiation. Together these data suggest that HSC cell surface HA is critical in their lodgement and subsequent quiescence within the hemopoietic stem cell niche.