Centre for Genomic Regulation and Universitat Pompeu Fabra, Barcelona, Spain.
Cell Cycle. 2012 Jan 1;11(1):39-47. doi: 10.4161/cc.11.1.18759.
Wnt/β-catenin canonical pathway has very important roles both in the regulation of self-renewal and lineage differentiation of pluripotent stem cells, as well as in the reprogramming of somatic cells. In the absence of Wnt stimulation, the target genes of the pathway are repressed or down-regulated. Conversely, when β-catenin is stabilized there is an accumulation of cytoplasmic and nuclear β-catenin that allows up-regulation of its target genes. However, the molecular mechanisms downstream of β-catenin that regulate self-renewal of embryonic stem cells remain unclear. It has been proposed that β-catenin acts through members of the T-cell factor (TCF) family. Recent studies have confirmed the role of Tcf3 (Tcf7l1) as a transcriptional repressor in embryonic stem cells, and they have also proposed a new mechanistic view as to how activation of the Wnt/β-catenin pathway can overcome this repression.
Wnt/β-catenin 经典途径在多能干细胞的自我更新和谱系分化的调控中以及体细胞重编程中具有非常重要的作用。在没有 Wnt 刺激的情况下,该途径的靶基因受到抑制或下调。相反,当 β-catenin 稳定时,细胞质和核内的 β-catenin 积累,允许其靶基因的上调。然而,β-catenin 调节胚胎干细胞自我更新的下游分子机制仍不清楚。有人提出,β-catenin 通过 T 细胞因子(TCF)家族的成员发挥作用。最近的研究证实了 Tcf3(Tcf7l1)作为胚胎干细胞中转录抑制剂的作用,并且它们还提出了一种新的机制观点,即 Wnt/β-catenin 途径的激活如何克服这种抑制。