Canonical Wnt pathway controls mESC self-renewal through inhibition of spontaneous differentiation via β-catenin/TCF/LEF functions
Canonical Wnt pathway controls mESC self-renewal through inhibition of spontaneous differentiation via β-catenin/TCF/LEF functions
Citació
- Aulicino F, Pedone E, Sottile F, Lluis F, Marucci L, Cosma MP. Canonical Wnt pathway controls mESC self-renewal through inhibition of spontaneous differentiation via β-catenin/TCF/LEF functions. Stem Cell Reports. 2020; 15(3):646-61. DOI: 10.1016/j.stemcr.2020.07.019
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Resum
The Wnt/β-catenin signaling pathway is a key regulator of embryonic stem cell (ESC) self-renewal and differentiation. Constitutive activation of this pathway has been shown to increase mouse ESC (mESC) self-renewal and pluripotency gene expression. In this study, we generated a novel β-catenin knockout model in mESCs to delete putatively functional N-terminally truncated isoforms observed in previous knockout models. We showed that aberrant N-terminally truncated isoforms are not functional in mESCs. In the generated knockout line, we observed that canonical Wnt signaling is not active, as β-catenin ablation does not alter mESC transcriptional profile in serum/LIF culture conditions. In addition, we observed that Wnt signaling activation represses mESC spontaneous differentiation in a β-catenin-dependent manner. Finally, β-catenin (ΔC) isoforms can rescue β-catenin knockout self-renewal defects in mESCs cultured in serum-free medium and, albeit transcriptionally silent, cooperate with TCF1 and LEF1 to inhibit mESC spontaneous differentiation in a GSK3-dependent manner.