Canonical Wnt Signaling Regulates Hematopoiesis in a Dosage-Dependent Fashion

Tiago Luis, Gita Naber, PPC Roozen, MH (Martijn) Brugman, EFE Haas, Mehrnaz Ghazvini, WE Fibbe, Jacques Dongen, Riccardo Fodde, Frank Staal

Research output: Contribution to journalArticleAcademic

227 Citations (Scopus)

Abstract

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.
Original languageUndefined/Unknown
Pages (from-to)345-356
Number of pages12
JournalCell Stem Cell
Volume9
Issue number4
DOIs
Publication statusPublished - 2011

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