Epithelial cadherin regulates transition between the naïve and primed pluripotent states in mouse embryonic stem cellsCitation formats

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Epithelial cadherin regulates transition between the naïve and primed pluripotent states in mouse embryonic stem cells. / Sharaireh, Aseel; Fitzpatrick, Loma M; Ward, Christopher; McKay, Tristan R; Unwin, Richard.

In: Stem Cells, Vol. 38, No. 10, 01.10.2020, p. 1292-1306.

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Sharaireh, Aseel ; Fitzpatrick, Loma M ; Ward, Christopher ; McKay, Tristan R ; Unwin, Richard. / Epithelial cadherin regulates transition between the naïve and primed pluripotent states in mouse embryonic stem cells. In: Stem Cells. 2020 ; Vol. 38, No. 10. pp. 1292-1306.

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@article{db57597c300247979d22aa16ca834a5a,
title = "Epithelial cadherin regulates transition between the na{\"i}ve and primed pluripotent states in mouse embryonic stem cells",
abstract = "Inhibition of E-cad in mouse embryonic stem cells (mESCs) leads to a switch from LIF-BMP to Activin/Nodal-dependent pluripotency, consistent with transition from a na{\"i}ve to primed pluripotent phenotype. We have used both genetic ablation and steric inhibition of E-cad function in mESCs to assess alterations to phenotype using Q6 quantitative MS/MS analysis, network models, and functional assays. Proteomic analyses revealed that one third of detected proteins were altered in E-cad null mESCs (Ecad−/− mESCs) compared to wild type (624 proteins were downregulated and 705 were proteins upregulated). Network pathway analysis and subsequent cellular flux assays confirmed a metabolic shift from oxidative phosphorylation (OXPHOS) to aerobic glycolysis, specifically through mitochondrial complex III downregulation and hypoxia inducible factor 1a target upregulation. Central to this was the transcriptionalcoactivator EP300. E-cad is a well-known tumor suppressor, its downregulation during cancer initiation and metastasis can be linked to the metabolic switch known as Warburg effect. This study highlights a phenomena found in both primed pluripotent state and cancer stemness and links it to loss of E-cad. Data are available via ProteomeXchange with identifier PXD012679.",
author = "Aseel Sharaireh and Fitzpatrick, {Loma M} and Christopher Ward and McKay, {Tristan R} and Richard Unwin",
year = "2020",
month = oct,
day = "1",
doi = "10.1002/stem.3249",
language = "English",
volume = "38",
pages = "1292--1306",
journal = "Stem Cells",
issn = "1066-5099",
publisher = "AlphaMed Press",
number = "10",

}

RIS

TY - JOUR

T1 - Epithelial cadherin regulates transition between the naïve and primed pluripotent states in mouse embryonic stem cells

AU - Sharaireh, Aseel

AU - Fitzpatrick, Loma M

AU - Ward, Christopher

AU - McKay, Tristan R

AU - Unwin, Richard

PY - 2020/10/1

Y1 - 2020/10/1

N2 - Inhibition of E-cad in mouse embryonic stem cells (mESCs) leads to a switch from LIF-BMP to Activin/Nodal-dependent pluripotency, consistent with transition from a naïve to primed pluripotent phenotype. We have used both genetic ablation and steric inhibition of E-cad function in mESCs to assess alterations to phenotype using Q6 quantitative MS/MS analysis, network models, and functional assays. Proteomic analyses revealed that one third of detected proteins were altered in E-cad null mESCs (Ecad−/− mESCs) compared to wild type (624 proteins were downregulated and 705 were proteins upregulated). Network pathway analysis and subsequent cellular flux assays confirmed a metabolic shift from oxidative phosphorylation (OXPHOS) to aerobic glycolysis, specifically through mitochondrial complex III downregulation and hypoxia inducible factor 1a target upregulation. Central to this was the transcriptionalcoactivator EP300. E-cad is a well-known tumor suppressor, its downregulation during cancer initiation and metastasis can be linked to the metabolic switch known as Warburg effect. This study highlights a phenomena found in both primed pluripotent state and cancer stemness and links it to loss of E-cad. Data are available via ProteomeXchange with identifier PXD012679.

AB - Inhibition of E-cad in mouse embryonic stem cells (mESCs) leads to a switch from LIF-BMP to Activin/Nodal-dependent pluripotency, consistent with transition from a naïve to primed pluripotent phenotype. We have used both genetic ablation and steric inhibition of E-cad function in mESCs to assess alterations to phenotype using Q6 quantitative MS/MS analysis, network models, and functional assays. Proteomic analyses revealed that one third of detected proteins were altered in E-cad null mESCs (Ecad−/− mESCs) compared to wild type (624 proteins were downregulated and 705 were proteins upregulated). Network pathway analysis and subsequent cellular flux assays confirmed a metabolic shift from oxidative phosphorylation (OXPHOS) to aerobic glycolysis, specifically through mitochondrial complex III downregulation and hypoxia inducible factor 1a target upregulation. Central to this was the transcriptionalcoactivator EP300. E-cad is a well-known tumor suppressor, its downregulation during cancer initiation and metastasis can be linked to the metabolic switch known as Warburg effect. This study highlights a phenomena found in both primed pluripotent state and cancer stemness and links it to loss of E-cad. Data are available via ProteomeXchange with identifier PXD012679.

U2 - 10.1002/stem.3249

DO - 10.1002/stem.3249

M3 - Article

VL - 38

SP - 1292

EP - 1306

JO - Stem Cells

JF - Stem Cells

SN - 1066-5099

IS - 10

ER -