期刊
STEM CELLS
卷 30, 期 9, 页码 1842-1851出版社
WILEY
DOI: 10.1002/stem.1148
关键词
E-cadherin; N-cadherin; beta-Catenin; Kruppel-like factor 4; Nanog; STAT3; Pluripotency; Embryonic stem cells
资金
- Biotechnology and Biological Sciences Research Council (BBSRC)
- Engineering and Physical Sciences Research Council
- BBSRC PhD studentship
- BBSRC [BB/E527239/1] Funding Source: UKRI
- EPSRC [EP/H046070/1, TS/G000646/1] Funding Source: UKRI
- MRC [G0701165] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/E527239/1] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [EP/H046070/1, TS/G000646/1] Funding Source: researchfish
- Medical Research Council [G0701165] Funding Source: researchfish
We have recently shown that loss of E-cadherin in mouse embryonic stem cells (mESCs) results in significant alterations to both the transcriptome and hierarchy of pluripotency-associated signaling pathways. Here, we show that E-cadherin promotes kruppel-like factor 4 (Klf4) and Nanog transcript and protein expression in mESCs via STAT3 phosphorylation and that beta-catenin, and its binding region in E-cadherin, is required for this function. To further investigate the role of E-cadherin in leukemia inhibitory factor (LIF)-dependent pluripotency, E-cadherin null (Ecad(-/-)) mESCs were cultured in LIF/bone morphogenetic protein supplemented medium. Under these condi-tions, Ecad(-/-) mESCs exhibited partial restoration of cell-cell contact and STAT3 phosphorylation and upregulated Klf4, Nanog, and N-cadherin transcripts and protein. Abrogation of N-cadherin using an inhibitory peptide caused loss of phospho STAT3, Klf4, and Nanog in these cells, demonstrating that N-cadherin supports LIF-dependent pluripotency in this context. We therefore identify a novel molecular mechanism linking E-and N-cadherin to the core circuitry of pluripotency in mESCs. This mechanism may explain the recently documented role of E-cadherin in efficient induced pluripotent stem cell reprogramming. STEM CELLS 2012;30:1842-1851
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据