Regulation of self-renewal and reprogramming by TCF factors

Abstract

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 downregulated. Conversely, when β-catenin is stabilized there is an accumulation of cytoplasmic and nuclear β-catenin that allows upregulation 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. © 2012 Landes Bioscience.