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Loss of Tcf7 diminishes hematopoietic stem/progenitor cell function

Leukemia volume 27, pages 1613–1614 (2013)Cite this article

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The canonical Wnt-β-catenin pathway is an evolutionarily conserved and tightly regulated pathway in development. Activation of this pathway occurs upon binding of a soluble Wnt protein to a membrane-associated receptor, and leads to the disruption and inhibition of a protein complex responsible for the phosphorylation and breakdown of β-catenin. Inhibition of this so-called destruction complex, composed of the tumor suppressor Apc, the Ser-Thr kinases Gsk-3β and CK-I, and the scaffold and tumor suppressor protein Axin, results in stabilization and (nuclear) accumulation of β-catenin. Stabilized β-catenin forms a bipartite transcription factor with the Tcf-Lef family of transcription factors (including Tcf7, Tcf7l1, Tcf7l2 and Lef1) to activate a Wnt-controlled gene expression program.1

In the hematopoietic system, a role for Wnt signaling was first demonstrated during T-cell development in the thymus.2 Subsequently, opposing effects of Wnt signaling on hematopoiesis have been reported. For example, Mx-Cre-mediated deletion of β- or β- and γ-catenin did not effect hematopoiesis, but stabilized forms of β-catenin resulted in either enhancement of hematopoietic stem cell (HSC) function and maintenance of an immature phenotype or exhaustion of the HSC pool.3, 4, 5, 6, 7, 8 These differences might be explained by different levels of Wnt pathway activation. By using various targeted hypomorphic Apc alleles and a conditional deletion allele of Apc, which generates different Wnt signaling levels, it has been shown that different, lineage-specific Wnt dosages regulate HSCs, myeloid precursors and T lymphoid precursors during hematopoiesis.9

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Authors and Affiliations

  1. Department of Haematology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    G Huls

  2. Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Centre Utrecht, Utrecht, The Netherlands

    J van Es & H Clevers

  3. Department of Biology of Aging, Section Stem Cell Biology, European Research Institute for the Biology of Aging (ERIBA), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    G de Haan & R van Os

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Correspondence to G Huls.

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Huls, G., van Es, J., Clevers, H. et al. Loss of Tcf7 diminishes hematopoietic stem/progenitor cell function. Leukemia 27, 1613–1614 (2013). https://doi.org/10.1038/leu.2012.354

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