The role of noncanonical and canonical Wnt signaling in activating and expanding hematopoietic stem cells (HSCs) in vivo has not been described in detail. Sugimura et al. performed a series of elegant experiments to demonstrate that quiescent HSCs are maintained by the expression of Flamingo and Frizzled, two components of the noncanonical Wnt pathway.
The two interact closely; Flamingo regulates how Frizzled is distributed at the interface between HSCs and osteoblasts that express N-cadherin, a protein that enriches osteoprogenitor cells. When homeostasis is being maintained, N-cadherin
The pathways involved are complex but the study suggests that Frizzled suppresses the Ca
Editor's comment: This study demonstrates that noncanonical Wnt signaling in N-cadherin-positive osteoblasts maintains quiescence of HSCs and antagonizes canonical Wnt signaling to activate HSCs. These observations provide important clues about how best to maintain or expand the use of HSCs in various disorders of hematopoiesis.