Epiblast Ground State Is Controlled by Canonical Wnt/β-Catenin Signaling in the Postimplantation Mouse Embryo and Epiblast Stem Cells

Sumi, Tomonori; Oki, Sadaaki; Kitajima, Kenji; Meno, Chikara

doi:10.1371/journal.pone.0063378

Cited by 101 publications

(120 citation statements)

References 53 publications

Supporting

Mentioning

111

Contrasting

Order By: Relevance

“…Homogenous primed-state mEpiSC lines can be more efficiently established in the presence of Wnt inhibitors, such as IWP2 (42) and XAV939 (43). Our mass spectrometry-based analysis of protein expression profiles of naïve ELF1 hESCs with inhibition of Wnt/ β-catenin signaling also suggests that blocking of Wnt/β-catenin signaling could lead naïve hESCs to a more primed-like state (Fig.…”

Section: Discussionmentioning

confidence: 73%

Wnt/β-catenin signaling promotes self-renewal and inhibits the primed state transition in naïve human embryonic stem cells

Robitaille

Berndt

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

111

View full text Add to dashboard Cite

In both mice and humans, pluripotent stem cells (PSCs) exist in at least two distinct states of pluripotency, known as the naïve and primed states. Our understanding of the intrinsic and extrinsic factors that enable PSCs to self-renew and to transition between different pluripotent states is important for understanding early development. In mouse embryonic stem cells (mESCs), Wnt proteins stimulate mESC self-renewal and support the naïve state. In human embryonic stem cells (hESCs), Wnt/β-catenin signaling is active in naïve-state hESCs and is reduced or absent in primed-state hESCs. However, the role of Wnt/β-catenin signaling in naïve hESCs remains largely unknown. Here, we demonstrate that inhibition of the secretion of Wnts or inhibition of the stabilization of β-catenin in naïve hESCs reduces cell proliferation and colony formation. Moreover, we show that addition of recombinant Wnt3a partially rescues cell proliferation in naïve hESCs caused by inhibition of Wnt secretion. Notably, inhibition of Wnt/β-catenin signaling in naïve hESCs did not cause differentiation. Instead, it induced primed hESC-like proteomic and metabolic profiles. Thus, our results suggest that naïve hESCs secrete Wnts that activate autocrine or paracrine Wnt/β-catenin signaling to promote efficient self-renewal and inhibit the transition to the primed state.Wnt/β-catenin signaling | naïve pluripotency | naïve-to-primed transition | human embryonic stem cells | self-renewal

show abstract

Section: Discussionmentioning

confidence: 73%

Wnt/β-catenin signaling promotes self-renewal and inhibits the primed state transition in naïve human embryonic stem cells

Robitaille

Berndt

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

111

View full text Add to dashboard Cite

show abstract

“…Although the effect of Wnt signaling in iNOS-induced drug resistance was confirmed in our experiment, the differences between canonical and noncanonical Wnt pathways in regulating the level of iNOS were still unclear. By treatment with Wnt/β-catenin inhibitor XAV939 (18,19), Wnt/Ca 2+ inhibitor XeC (20,21) and Wnt/JNK inhibitor SP600125 respectively in A549/CDDP, we found a lower iNOS and GST-π, and a higher TOPO IIα in the Wnt/β-catenin-blocking group. However, neither Wnt/JNK nor Wnt/Ca 2+ pathway were correlated with iNOS, GST-π and TOPO IIα as shown in Fig.…”

Section: Resultsmentioning

confidence: 81%

Effect of nitric oxide synthase on multiple drug resistance is related to Wnt signaling in non-small cell lung cancer

et al. 2014

Oncology Reports

View full text Add to dashboard Cite

Multiple drug resistance (MDR) is considered a major challenge in the clinical treatment of non-small cell lung cancer (NSCLC). Both nitric oxide synthase (iNOS) and Wnt signaling pathway participate in the regulation of drug resistance, but the interaction between them remains unclear. In the present study, we detected the activation of Wnt/β-catenin signaling in iNOS-induced drug-resistant lung cancer cells, and compared the effect of canonical and noncanonical Wnt pathway on the level of iNOS. Moreover, we investigated the expression of Wnt/β-catenin signaling downstream factors and its main inhibitors. The results indicated iNOS-induced drug resistance was possibly mediated by glutathione S-transferase-π (GST-π) and topoisomerase IIα (TOPO IIα), but not P-glycoprotein (P-gp), and this process was closely associated with the activation of canonical Wnt/β-catenin signaling, but less with noncanonical pathways. The mechanism of iNOS promoting Wnt/β-catenin pathway was mainly dependent on the inverse regulation of Dickkopf-1 (DKK-1) and secreted frizzled-related protein-1 (SFRP-1). Clarifying the relationship between iNOS and Wnt signaling may provide insight into a better understanding of the mechanism of drug resistance development in NSCLC.

show abstract

“…4A). Next, we established EpiSCs from E6.5 embryos using N2B27-based medium supplemented with activin A, basic fibroblast growth factor and the Wnt signalling inhibitor, XAV939 (Sumi et al, 2013) and confirmed that the established cells were in a primed state by examining several markers; alkaline phosphatase staining confirmed that signals in EpiSCs were weaker than in ESCs (Fig. S4A).…”

Section: /Hprtmentioning

confidence: 75%

Live imaging of X chromosome reactivation dynamics in early mouse development can discriminate naïve from primed pluripotent stem cells

et al. 2016

View full text Add to dashboard Cite

Pluripotent stem cells can be classified into two distinct states, naïve and primed, which show different degrees of potency. One difficulty in stem cell research is the inability to distinguish these states in live cells. Studies on female mice have shown that reactivation of inactive X chromosomes occurs in the naïve state, while one of the X chromosomes is inactivated in the primed state. Therefore, we aimed to distinguish the two states by monitoring X chromosome reactivation. Thus far, X chromosome reactivation has been analysed using fixed cells; here, we inserted different fluorescent reporter gene cassettes (mCherry and eGFP) into each X chromosome. Using these knock-in 'Momiji' mice, we detected X chromosome reactivation accurately in live embryos, and confirmed that the pluripotent states of embryos were stable ex vivo, as represented by embryonic and epiblast stem cells in terms of X chromosome reactivation. Thus, Momiji mice provide a simple and accurate method for identifying stem cell status based on X chromosome reactivation.

show abstract

Epiblast Ground State Is Controlled by Canonical Wnt/β-Catenin Signaling in the Postimplantation Mouse Embryo and Epiblast Stem Cells

Cited by 101 publications

References 53 publications

Wnt/β-catenin signaling promotes self-renewal and inhibits the primed state transition in naïve human embryonic stem cells

Wnt/β-catenin signaling promotes self-renewal and inhibits the primed state transition in naïve human embryonic stem cells

Effect of nitric oxide synthase on multiple drug resistance is related to Wnt signaling in non-small cell lung cancer

Live imaging of X chromosome reactivation dynamics in early mouse development can discriminate naïve from primed pluripotent stem cells

Contact Info

Product

Resources

About