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Title: Non-canonical Wnt signaling maintains hematopoietic stem cell through Flamingo and Frizzled8 interaction in the niche
Author: Sugimura, Ryohichi
ISNI:       0000 0004 2742 1315
Awarding Body: Open University
Current Institution: Open University
Date of Award: 2012
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Wnt signaling is involved in self-renewal and maintenance of hematopoietic 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+-NFAT-IFNγ pathway and antagonizes canonical Wnt signaling in HSCs. My findings demonstrate that non-canonical Wnt signaling maintains quiescent longterm HSCs through Flamingo and Frizzled8 interaction in the niche.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral