Noncanonical Wnt signaling maintains hematopoietic stem cells in the niche

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

Research output: Contribution to journalArticle

155 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)351-365
Number of pages15
JournalCell
Volume150
Issue number2
DOIs
StatePublished - Jul 20 2012

Fingerprint

Stem Cell Niche
Hematopoietic Stem Cells
Stem cells
Cadherins
Osteoblasts
Homeostasis
Maintenance
Ligands
Chemical activation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Sugimura, R., He, X. C., Venkatraman, A., Arai, F., Box, A., Semerad, C. L., ... Li, L. (2012). Noncanonical Wnt signaling maintains hematopoietic stem cells in the niche. Cell, 150(2), 351-365. https://doi.org/10.1016/j.cell.2012.05.041

Noncanonical Wnt signaling maintains hematopoietic stem cells in the niche. / Sugimura, Ryohichi; He, Xi C.; Venkatraman, Aparna; Arai, Fumio; Box, Andrew; Semerad, Craig L; Haug, Jeffrey S.; Peng, Lai; Zhong, Xiao Bo; Suda, Toshio; Li, Linheng.

In: Cell, Vol. 150, No. 2, 20.07.2012, p. 351-365.

Research output: Contribution to journalArticle

Sugimura, R, He, XC, Venkatraman, A, Arai, F, Box, A, Semerad, CL, Haug, JS, Peng, L, Zhong, XB, Suda, T & Li, L 2012, 'Noncanonical Wnt signaling maintains hematopoietic stem cells in the niche', Cell, vol. 150, no. 2, pp. 351-365. https://doi.org/10.1016/j.cell.2012.05.041
Sugimura, Ryohichi ; He, Xi C. ; Venkatraman, Aparna ; Arai, Fumio ; Box, Andrew ; Semerad, Craig L ; Haug, Jeffrey S. ; Peng, Lai ; Zhong, Xiao Bo ; Suda, Toshio ; Li, Linheng. / Noncanonical Wnt signaling maintains hematopoietic stem cells in the niche. In: Cell. 2012 ; Vol. 150, No. 2. pp. 351-365.
@article{14dbf269054343ff9e39d81a1da98d26,
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 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.",
author = "Ryohichi Sugimura and He, {Xi C.} and Aparna Venkatraman and Fumio Arai and Andrew Box and Semerad, {Craig L} and Haug, {Jeffrey S.} and Lai Peng and Zhong, {Xiao Bo} and Toshio Suda and Linheng Li",
year = "2012",
month = "7",
day = "20",
doi = "10.1016/j.cell.2012.05.041",
language = "English (US)",
volume = "150",
pages = "351--365",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - Noncanonical Wnt signaling maintains hematopoietic stem cells in the niche

AU - Sugimura, Ryohichi

AU - He, Xi C.

AU - Venkatraman, Aparna

AU - Arai, Fumio

AU - Box, Andrew

AU - Semerad, Craig L

AU - Haug, Jeffrey S.

AU - Peng, Lai

AU - Zhong, Xiao Bo

AU - Suda, Toshio

AU - Li, Linheng

PY - 2012/7/20

Y1 - 2012/7/20

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84864194496&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864194496&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2012.05.041

DO - 10.1016/j.cell.2012.05.041

M3 - Article

VL - 150

SP - 351

EP - 365

JO - Cell

JF - Cell

SN - 0092-8674

IS - 2

ER -