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


  • G. Jeannet
  • M. Scheller
  • L. Scarpellino
  • S. Duboux
  • N. Gardiol
  • J. Back
  • F. Kuttler
  • I. Malanchi
  • W. Birchmeier
  • A. Leutz
  • J. Huelsken
  • W. Held


  • Blood


  • Blood 111 (1): 142-149


  • 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 TCF/LEF 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 (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 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.