Jeannet, G.Scheller, M.Scarpellino, L.Duboux, S.Gardiol, N.Back, J.Kuttler, F.Malanchi, I.Birchmeier, W.Leutz, A.Huelsken, J.Held, W.2008-02-182008-02-182008-02-18200810.1182/blood-2007-07-102558https://infoscience.epfl.ch/handle/20.500.14299/18801WOS:00025200200002412012The 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.Long-term, multilineage hematopoiesis occurs in the combined absence of beta-catenin and gamma-catenintext::journal::journal article::research article