title: Noncanonical Wnt signaling maintains hematopoietic stem cells in the niche.
abstract: Wnt signaling is involved in self-renewal and maintenance of hematopoietic stem cells (HSCs); however, the particular role of noncanonical Wnt signaling in regulating HSCs in vivo is largely unknown. Here, we show Flamingo (Fmi) and Frizzled (Fz) 8, members of noncanonical Wnt signaling, both express in and functionally maintain quiescent long-term HSCs. Fmi regulates Fz8 distribution at the interface between HSCs and N-cadherin(+) osteoblasts (N-cad(+)OBs that enrich osteoprogenitors) in the niche. We further found that N-cad(+)OBs predominantly express noncanonical Wnt ligands and inhibitors of canonical Wnt signaling under homeostasis. Under stress, noncanonical Wnt signaling is attenuated and canonical Wnt signaling is enhanced in activation of HSCs. Mechanistically, noncanonical Wnt signaling mediated by Fz8 suppresses the Ca(2+)-NFAT- IFNγ pathway, directly or indirectly through the CDC42-CK1α complex and also antagonizes canonical Wnt signaling in HSCs. Taken together, our findings demonstrate that noncanonical Wnt signaling maintains quiescent long-term HSCs through Fmi and Fz8 interaction in the niche.
authors: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
authors: Ryohichi
authors: R
authors: Sugimura
authors: Xi C
authors: XC
authors: He
authors: Aparna
authors: A
authors: Venkatraman
authors: Fumio
authors: F
authors: Arai
authors: Andrew
authors: A
authors: Box
authors: Craig
authors: C
authors: Semerad
authors: Jeffrey S
authors: JS
authors: Haug
authors: Lai
authors: L
authors: Peng
authors: Xiao-Bo
authors: XB
authors: Zhong
authors: Toshio
authors: T
authors: Suda
authors: Linheng
authors: L
authors: Li
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D050778:NFATC Transcription Factors / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D055153:Stem Cell Niche; D060449:Wnt Signaling Pathway
chemical_list: D015820:Cadherins; D007371:Interferon-gamma; D050778:NFATC Transcription Factors; D043562:Receptors, G-Protein-Coupled; C498478:Celsr2 protein, mouse; C511610:Fzd8 protein, mouse