Canonical wnt signaling regulates hematopoiesis in a dosage-dependent fashion.
| Autor: | Luis TC; Department of Immunology, Erasmus University Medical Center, The Netherlands., Naber BA, Roozen PP, Brugman MH, de Haas EF, Ghazvini M, Fibbe WE, van Dongen JJ, Fodde R, Staal FJ |
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| Jazyk: | angličtina |
| Zdroj: | Cell stem cell [Cell Stem Cell] 2011 Oct 04; Vol. 9 (4), pp. 345-56. |
| DOI: | 10.1016/j.stem.2011.07.017 |
| Abstrakt: | Canonical Wnt signaling has been implicated in the regulation of hematopoiesis. By employing a Wnt-reporter mouse, we observed that Wnt signaling is differentially activated during hematopoiesis, suggesting an important regulatory role for specific Wnt signaling levels. To investigate whether canonical Wnt signaling regulates hematopoiesis in a dosage-dependent fashion, we analyzed the effect of different mutations in the Adenomatous polyposis coli gene (Apc), a negative modulator of the canonical Wnt pathway. By combining different targeted hypomorphic alleles and a conditional deletion allele of Apc, a gradient of five different Wnt signaling levels was obtained in vivo. We here show that different, lineage-specific Wnt dosages regulate hematopoietic stem cells (HSCs), myeloid precursors, and T lymphoid precursors during hematopoiesis. Differential, lineage-specific optimal Wnt dosages provide a unifying concept that explains the differences reported among inducible gain-of-function approaches, leading to either HSC expansion or depletion of the HSC pool. (Copyright © 2011 Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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