Connexin 43 is involved in early differentiation of human embryonic stem cells

Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which mediates the effects of a variety of environmental stimuli in multiple tissues. Recent advances in AHR biology have underlined its importance in cells with high developmental potency, including pluripotent stem cells. Nonetheless, there is little data on AHR expression and its role during the initial stages of stem cell differentiation. The purpose of this study was to investigate the temporal pattern of AHR expression during directed differentiation of human embryonic stem cells (hESC) into neural progenitor, early mesoderm and definitive endoderm cells. Additionally, we investigated the effect of the AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the gene expression profile in hESCs and differentiated cells by RNA-seq, accompanied by identification of AHR binding sites by ChIP-seq and epigenetic landscape analysis by ATAC-seq. We showed that AHR is differentially regulated in distinct lineages. We provided evidence that TCDD alters gene expression patterns in hESCs and during early differentiation. Additionally, we identified novel potential AHR target genes, which expand our understanding on the role of this protein in different cell types.

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Downregulation of E-cadherin in pluripotent stem cells triggers partial EMT

10.1101/2020.05.18.101899 ◽

2020 ◽

Author(s):

C. Aban ◽

A. Lombardi ◽

G. Neiman ◽

M.C. Biani ◽

A. La Greca ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Human Embryonic Stem Cells ◽

Connexin 43 ◽

Cancer Metastasis ◽

Embryonic Stem ◽

Stem Cell Differentiation ◽

Embryonic Stem Cell Differentiation ◽

Mesenchymal Transition ◽

E Cadherin

Epithelial to mesenchymal transition (EMT) is a critical cellular process that has been well characterized during embryonic development and cancer metastasis and it also is implicated in several physiological and pathological events including embryonic stem cell differentiation. During early stages of differentiation, human embryonic stem cells pass through EMT where deeper morphological, molecular and biochemical changes occur. Though initially considered as a decision between two states, EMT process is now regarded as a fluid transition where cells exist on a spectrum of intermediate states. In this work, using a CRISPR interference system in human embryonic stem cells, we describe a molecular characterization of the effects of downregulation of E-cadherin, one of the main initiation events of EMT, as a unique start signal. Our results suggest that the decrease and delocalization of E-cadherin causes an incomplete EMT where cells retain their undifferentiated state while expressing several characteristics of a mesenchymal-like pheno-type. Namely, we found that E-cadherin downregulation induces SNAI1 and SNAI2 upregulation, promotes MALAT1 and LINC-ROR downregulation, modulates the expression of tight junction occludin 1 and gap junction connexin 43, increases human embryonic stem cells migratory capacity and delocalize b-catenin. Altogether, we believe our results provide a useful tool to model the molecular events of an unstable intermediate state and further identify multiple layers of molecular changes that occur during partial EMT.

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Effect of low dose bisphenol A on the early differentiation of human embryonic stem cells into mammary epithelial cells

Toxicology Letters ◽

10.1016/j.toxlet.2013.01.026 ◽

2013 ◽

Vol 218 (3) ◽

pp. 187-193 ◽

Cited By ~ 35

Author(s):

Linqing Yang ◽

Lingfeng Luo ◽

Weidong Ji ◽

Chunmei Gong ◽

Desheng Wu ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Epithelial Cells ◽

Bisphenol A ◽

Human Embryonic Stem Cells ◽

Low Dose ◽

Mammary Epithelial Cells ◽

Embryonic Stem ◽

Mammary Epithelial ◽

Early Differentiation

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Red Ginseng Extract Facilitates the Early Differentiation of Human Embryonic Stem Cells into Mesendoderm Lineage

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2011/167376 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Yoon Young Kim ◽

Seung-Yup Ku ◽

Zev Rosenwaks ◽

Hung Ching Liu ◽

Sun Kyung Oh ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Human Embryonic Stem Cells ◽

Embryonic Stem ◽

Embryoid Bodies ◽

Red Ginseng ◽

Cardiac Progenitors ◽

Early Differentiation ◽

Undifferentiated Hescs ◽

Wide Range

Human embryonic stem cells (hESCs) have capacities to self-renew and differentiate into all cell typesin vitro. Red ginseng (RG) is known to have a wide range of pharmacological effectsin vivo; however, the reports on its effects on hESCs are few. In this paper, we tried to demonstrate the effects of RG on the proliferation and differentiation of hESCs. Undifferentiated hESCs, embryoid bodies (EBs), and hESC-derived cardiac progenitors (CPs) were treated with RG extract at 0.125, 0.25, and 0.5 mg/mL. After treatment of undifferentiated hESCs from day 2 to day 6 of culture, BrdU labeling showed that RG treatment increased the proliferation of hESCs, and the expression of Oct4 and Nanog was increased in RG-treated group. To find out the effects of RG on early differentiation stage cells, EBs were treated with RG extract for 10 days and attached for further differentiation. Immunostaining for three germ layer markers showed that RG treatment increased the expressions of Brachyury and HNF3βon EBs. Also, RG treatment increased the expression of Brachyury in early-stage and of Nkx2.5 in late-stage hESC-derived CPs. These results demonstrate facilitating effects of RG extract on the proliferation and early differentiation of hESC.

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