Long-term, multilineage hematopoiesis occurs in the combined absence of beta-catenin and gamma-catenin - PubMed (original) (raw)

. 2008 Jan 1;111(1):142-9.

doi: 10.1182/blood-2007-07-102558. Epub 2007 Sep 28.

Marina Scheller, Léonardo Scarpellino, Stéphane Duboux, Noemie Gardiol, Jonathan Back, Fabien Kuttler, Ilaria Malanchi, Walter Birchmeier, Achim Leutz, Joerg Huelsken, Werner Held

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Long-term, multilineage hematopoiesis occurs in the combined absence of beta-catenin and gamma-catenin

Grégoire Jeannet et al. Blood. 2008.

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Abstract

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.

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