Journal
DEVELOPMENT
Volume 140, Issue 6, Pages 1171-1183Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.085654
Keywords
Oct4; Wnt signaling; Mouse embryonic stem cells; Pluripotency; beta-Catenin
Categories
Funding
- Wellcome Trust
- European Research Council
- Human Frontier Science Program
- Herchel Smith postdoctoral fellowship
- Postdoctoral fellowship Beca Chile [74100037]
- New York State Stem Cell Medicine (NYSTEM) Post-doctoral training fellowship
- Biotechnology and Biological Sciences Research Council (BBSRC) [BB/D526088/1]
- National Institutes of Health [1R21HD057525-01]
- NYSTEM
- BBSRC [BB/D526088/1] Funding Source: UKRI
Ask authors/readers for more resources
The maintenance of pluripotency in mouse embryonic stem cells (mESCs) relies on the activity of a transcriptional network that is fuelled by the activity of three transcription factors (Nanog, Oct4 and Sox2) and balanced by the repressive activity of Tcf3. Extracellular signals modulate the activity of the network and regulate the differentiation capacity of the cells. Wnt/beta-catenin signaling has emerged as a significant potentiator of pluripotency: increases in the levels of beta-catenin regulate the activity of Oct4 and Nanog, and enhance pluripotency. A recent report shows that beta-catenin achieves some of these effects by modulating the activity of Tcf3, and that this effect does not require its transcriptional activation domain. Here, we show that during self-renewal there is negligible transcriptional activity of beta-catenin and that this is due to its tight association with membranes, where we find it in a complex with Oct4 and E-cadherin. Differentiation triggers a burst of Wnt/beta-catenin transcriptional activity that coincides with the disassembly of the complex. Our results establish that beta-catenin, but not its transcriptional activity, is central to pluripotency acting through a beta-catenin/Oct4 complex.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available