Nature Immunology
- 7, 1037 - 1047 (2006)
Published online: 3 September 2006; | doi:10.1038/ni1387
Hematopoietic stem cell and multilineage defects generated by constitutive  -catenin activationMarina Scheller1, Joerg Huelsken2, Frank Rosenbauer1, Makoto M Taketo3, Walter Birchmeier1, 4, Daniel G Tenen5 & Achim Leutz1, 41
Max-Delbrück Center for Molecular Medicine, 13125 Berlin, Germany. 2
Ecole Polytechnique Fédérale de Lausanne, Institut Suisse de Recherche Expérimentale sur le Cancer, 1066 Epalinges, Switzerland. 3
Department of Pharmacology, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan. 4
Humboldt-University Berlin, 10099 Berlin, Germany. 5
Harvard Institutes of Medicine and Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA.
Correspondence should be addressed to Achim Leutz aleutz@mdc-berlin.de Gain of Wnt signaling through  -catenin has been ascribed a critical function in the stimulation of hematopoietic stem cell self-renewal, whereas loss of -catenin is reportedly dispensable for hematopoiesis. Here we have used conditional mouse genetics and transplantation assays to demonstrate that constitutive activation of -catenin blocked multilineage differentiation, leading to the death of mice. Blood cell depletion was accompanied by failure of hematopoietic stem cells to repopulate irradiated hosts and to differentiate into mature cells. Activation of -catenin enforced cell cycle entry of hematopoietic stem cells, thus leading to exhaustion of the long-term stem cell pool. Our data suggest that fine-tuned Wnt stimulation is essential for hematopoiesis and is thus critical for therapeutic hematopoietic stem cell population expansion.
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