Hematopoietic stem cells (HSCs) are localized in a discrete bone marrow microenvironment termed niche, which is critical for their maintenance and regulation. We have initially identified the spindle-shaped N-cadherin+ bone lining cells in the endosteal zone of trabecular bone as a key component of the HSC niche, which is dominated by BMP and non-canonical WNT signals (Zhang et al 2003 Nature, Xie et al 2009 Nature, Sugimura et al 2012 Cell). Recently, we found that mature megakaryocytes constitute a critical niche for HSC regulation through balancing TGFβ and FGF signals (Zhao et al 2014 Nat Med). Now we are attempting to systematically study the distinct and complementary functions of different types of niche components in regulating different stages of HSCs and their lineage commitment.
Neonatal bone: Endosteal niche cells (red) lining both the bone surface and next to epiphyseal plate comprised of growing cartilages (green).
Image by Fang Tao.
A hematopoietic stem cell (green) attaches to a megakaryocyte (red) in mouse bone marrow.
Image by Meng Zhao.