Long-term, multilineage hematopoiesis occurs in the combined absence of beta-catenin and gamma-catenin.
The canonical Wnt signaling pathway plays key roles in stem-cell maintenance, progenitor cell expansion, and lineage decisions. Transcriptional responses induced by Wnt depend on the association of either beta-catenin or gamma-catenin with lymphoid enhancer factor/T cell factor transcription factors. Here we show that hematopoiesis, including thymopoiesis, is normal in the combined absence of beta- and gamma-catenin. Double-deficient hematopoietic stem cells maintain long-term repopulation capacity and multilineage differentiation potential. Unexpectedly, 2 independent ex vivo reporter gene assays show that Wnt signal transmission is maintained in double-deficient hematopoietic stem cells, thymocytes, or peripheral T cells. In contrast, Wnt signaling is strongly reduced in thymocytes lacking TCF-1 or in nonhematopoietic cells devoid of beta-catenin. These data provide the first evidence that hematopoietic cells can transduce canonical Wnt signals in the combined absence of beta- and gamma-catenin.
Jeannet
Grégoire
G
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland.
Scheller
Marina
M
Scarpellino
Léonardo
L
Duboux
Stéphane
S
Gardiol
Noemie
N
Back
Jonathan
J
Kuttler
Fabien
F
Malanchi
Ilaria
I
Birchmeier
Walter
W
Leutz
Achim
A
Huelsken
Joerg
J
Held
Werner
W
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D019070:Cell Lineage / Q000502:physiology*; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006825:Hybridomas; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000502:physiology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology*; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism; D051185:gamma Catenin / Q000235:genetics* / Q000378:metabolism
C495267:CTNNB1 protein, mouse; D051153:Wnt Proteins; D051176:beta Catenin; D051185:gamma Catenin