Mouse embryonic stem cells that survive γ-rays exposure maintain pluripotent differentiation potential and genome stability

Ethephon, a member of the organophosphorus compounds, is one of the most widely used plant growth regulators for artificial ripening. Although million pounds of this chemical is being used annually, the knowledge regarding its molecular toxicity is yet not sufficient. The purpose of this study was to evaluate the potential developmental toxicity of ethephon using embryonic stem cell model. The mouse embryonic stem cells (mESCs) were exposed to various concentrations of ethephon and the viability, cell cycle alteration and changes in the gene expression profile were evaluated using high-throughput RNA sequencing. Further, the effect of ethephon on neural differentiation potential was examined. The results showed that ethephon at noncytotoxic doses induced cell cycle arrest in mESCs. Gene ontology enrichment analysis showed that terms related to cell fate and organismal development, including neuron fate commitment, embryo development and cardiac cell differentiation, were markedly enriched in ethephon-treated cells. Neural induction of mESCs in the presence of ethephon was inhibited and the expression of neural genes was decreased in differentiated cells. Results obtained from this work clearly demonstrate that ethephon affects the gene expression profile of undifferentiated mESCs and prevents neural differentiation. Therefore, more caution against the frequent application of ethephon is advised.

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Tcea3 Regulates the Vascular Differentiation Potential of Mouse Embryonic Stem Cells

Gene Expression ◽

10.3727/105221613x13776146743343 ◽

2013 ◽

Vol 16 (1) ◽

pp. 25-30 ◽

Cited By ~ 6

Author(s):

Young Cha ◽

Sun-Hee Heo ◽

Hee-Jin Ahn ◽

Seong Kyu Yang ◽

Ji-Hwan Song ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Embryonic Stem ◽

Mouse Embryonic Stem Cells ◽

Vascular Differentiation ◽

Differentiation Potential

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Differentiation Potential of Mouse Embryonic Stem Cells into Insulin Producing Cells in Pancreatic Islet Microenvironment

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0035-1554720 ◽

2015 ◽

Vol 124 (02) ◽

pp. 120-129

Author(s):

I. Yilmaz ◽

A. Sariboyaci ◽

C. Subasi ◽

E. Karaoz

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Pancreatic Islet ◽

Embryonic Stem ◽

Mouse Embryonic Stem Cells ◽

Differentiation Potential ◽

Insulin Producing Cells

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Mobilization of LINE-1 retrotransposons is restricted by Tex19.1 in mouse embryonic stem cells

eLife ◽

10.7554/elife.26152 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 21

Author(s):

Marie MacLennan ◽

Marta García-Cañadas ◽

Judith Reichmann ◽

Elena Khazina ◽

Gabriele Wagner ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Translational Regulation ◽

Genome Stability ◽

De Novo ◽

Genetic Disorders ◽

Embryonic Stem ◽

Mouse Embryonic Stem Cells ◽

Dna Hypomethylation ◽

Genomic Locations

Mobilization of retrotransposons to new genomic locations is a significant driver of mammalian genome evolution, but these mutagenic events can also cause genetic disorders. In humans, retrotransposon mobilization is mediated primarily by proteins encoded by LINE-1 (L1) retrotransposons, which mobilize in pluripotent cells early in development. Here we show that TEX19.1, which is induced by developmentally programmed DNA hypomethylation, can directly interact with the L1-encoded protein L1-ORF1p, stimulate its polyubiquitylation and degradation, and restrict L1 mobilization. We also show that TEX19.1 likely acts, at least in part, through promoting the activity of the E3 ubiquitin ligase UBR2 towards L1-ORF1p. Moreover, loss of Tex19.1 increases L1-ORF1p levels and L1 mobilization in pluripotent mouse embryonic stem cells, implying that Tex19.1 prevents de novo retrotransposition in the pluripotent phase of the germline cycle. These data show that post-translational regulation of L1 retrotransposons plays a key role in maintaining trans-generational genome stability in mammals.

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