Noncanonical Wnt signaling maintains hematopoietic stem cells in the niche

Ryohichi Sugimura, Xi C. He, Aparna Venkatraman, Fumio Arai, Andrew Box, Craig Semerad, Jeffrey S. Haug, Lai Peng, Xiao Bo Zhong, Toshio Suda, Linheng Li

研究成果: Contribution to journalArticle査読

185 被引用数 (Scopus)

抄録

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 Ca2+-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.

本文言語英語
ページ(範囲)351-365
ページ数15
ジャーナルCell
150
2
DOI
出版ステータス出版済み - 7 20 2012
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学、遺伝学、分子生物学(全般)

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