Understanding the mechanisms regulating cell cycle, proliferation and potency of 
pluripotent stem cells guarantees their safe use in the clinic. Embryonic stem 
cells (ESCs) present a fast cell cycle with a short G1 phase. This is due to the 
lack of expression of cell cycle inhibitors, which ultimately determines naïve 
pluripotency by holding back differentiation. The canonical Wnt/β-catenin 
pathway controls mESC pluripotency via the Wnt-effector Tcf3. However, if the 
activity of the Wnt/β-catenin controls the cell cycle of mESCs remains unknown. 
Here we show that the Wnt-effector Tcf1 is recruited to and triggers 
transcription of the Ink4/Arf tumor suppressor locus. Thereby, the activation of 
the Wnt pathway, a known mitogenic pathway in somatic tissues, restores G1 phase 
and drastically reduces proliferation of mESCs without perturbing pluripotency. 
Tcf1, but not Tcf3, is recruited to a palindromic motif enriched in the promoter 
of cell cycle repressor genes, such as p15Ink4b, p16Ink4a and p19Arf, which 
mediate the Wnt-dependent anti-proliferative effect in mESCs. Consistently, 
ablation of β-catenin or Tcf1 expression impairs Wnt-dependent cell cycle 
regulation. All together, here we showed that Wnt signaling controls mESC 
pluripotency and proliferation through non-overlapping functions of distinct Tcf 
factors.