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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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Submitted July 25, 2007
Accepted September 24, 2007
Long-term, multilineage hematopoiesis occurs in the combined absence of -catenin and -catenin
Gregoire Jeannet, Marina Scheller, Leonardo Scarpellino, Stephane Duboux, Noemie Gardiol, Jonathan Back, Fabien Kuttler, Ilaria Malanchi, Walter Birchmeier, Achim Leutz, Joerg Huelsken, and Werner Held*
Lausanne Branch, Ludwig Institute for Cancer Research, Epalinges, Switzerland
Max-Delbruck Center for Molecular Medicine, Berlin, Germany
Swiss Institute for Experimental Cancer Research, Ecole Polytechnique Federale de Lausanne, Epalinges, Switzerland
* Corresponding author; email: werner.held{at}isrec.unil.ch.
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 -catenin or -catenin with TCF/LEF transcription factors. Here we show that hematopoiesis, including thymopoiesis, is normal in the combined absence of - and -catenin. Double-deficient hematopoietic stem cells (HSCs) maintain long-term repopulation capacity and multi lineage differentiation potential. Unexpectedly, two independent ex vivo reporter gene assays show that Wnt signal transmission is maintained in double-deficient HSCs, thymocytes, or peripheral T cells. In contrast, Wnt signaling is strongly reduced in thymocytes lacking TCF-1 or in non-hematopoietic cells devoid of -catenin. These data provide the first evidence that hematopoietic cells can transduce canonical Wnt signals in the combined absence of - and -catenin.

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