Wnt signaling is involved in self-renewal and maintenance ofhematopoietic stem cells (HSCs); however, the particular role of non-canonical Wnt signaling in regulating HSCs in vivo is largely unknown. Here I show Flamingo and Frizzled8, members of non-canonical Wnt signaling, both express in and functionally maintain quiescent long-term HSCs. Flamingo regulates Frizzled8 distribution at the interface between HSCs and N-cadherin + osteoblasts (N-cad+OBs that enrich osteoprogenitors) in the niche. I further show that N-cad+OBs predominantly express non-canonical Wnt ligands and inhibitors of canonical Wnt signaling under homeostasis. This non-canonical Wnt signaling is attenuated prior to activation of HSCs. In the activated HSCs, however, canonical Wnt signaling is enhanced. Mechanistically, non-canonical Wnt signaling mediated by Frizzled8 suppresses the Ca2+-NF AT- IFNy pathway and antagonizes canonical Wnt signaling in HSCs. My findings demonstrate that non-canonical Wnt signaling maintains quiescent long- term HSCs through Flamingo and Frizzled8 interaction in the niche.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:580673 |
| Date | January 2012 |
| Creators | Sugimura, Ryohichi |
| Publisher | Open University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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