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Blood, 1 January 2008, Vol. 111, No. 1, pp. 142-149.
Prepublished online as a Blood First Edition Paper on September 28, 2007; DOI 10.1182/blood-2007-07-102558.
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HEMATOPOIESIS
Long-term, multilineage hematopoiesis occurs in the combined absence of β-catenin and -catenin
Grégoire Jeannet1,
Marina Scheller2,
Léonardo Scarpellino1,
Stéphane Duboux3,
Noemie Gardiol1,
Jonathan Back1,
Fabien Kuttler3,
Ilaria Malanchi3,
Walter Birchmeier2,
Achim Leutz2,
Joerg Huelsken3, and
Werner Held1
1 Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland;
2 Max-Delbrück Center for Molecular Medicine, Berlin, Germany; and
3 Ecole Polytechnique Fédérale de Lausanne, Swiss Institute for Experimental Cancer Research, Lausanne, Switzerland
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 β-catenin or -catenin with lymphoid enhancer factor/T cell factor transcription factors. Here we show that hematopoiesis, including thymopoiesis, is normal in the combined absence of β- and -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 β-catenin. These data provide the first evidence that hematopoietic cells can transduce canonical Wnt signals in the combined absence of β- and -catenin.

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