Alteration of the N6-methyladenosine epitranscriptomic profile in synthetic phthalate-treated human induced pluripotent stem cell-derived endothelial cells

Plain language summary Synthetic phthalates, such as mono(2-ethyhexyl) phthalate, have long been recognized as environmental toxins. What effect these compounds have on endothelial cells remains poorly understood. To address this, the authors utilized a human-induced pluripotent stem cell-derived endothelial cell model to screen for an environmental toxin. They then obtained a profile of the epitranscriptomic changes involving the N-6-methyladensosine modification and performed biochemical and functional assays. Overall, this study demonstrated how stem cell-based approaches can be used for toxicological screening and provided a valuable resource that profiles the epitranscriptomic response, which was complemented with RNA sequencing and functional and biochemical assays. This study provides relevant toxicological insights into the context of human health. Background: This study aimed to characterize the N-6-methyladenosine epitranscriptomic profile induced by mono(2-ethylhexyl) phthalate (MEHP) exposure using a human-induced pluripotent stem cell-derived endothelial cell model. Methods: A multiomic approach was employed by performing RNA sequencing in parallel with an N-6-methyladenosine-specific microarray to identify mRNAs, lncRNAs, and miRNAs affected by MEHP exposure. Results: An integrative multiomic analysis identified relevant biological features affected by MEHP, while functional assays provided a phenotypic characterization of these effects. Transcripts regulated by the epitranscriptome were validated with quantitative PCR and methylated RNA immunoprecipitation. Conclusion: The authors' profiling of the epitranscriptome expands the scope of toxicological insights into known environmental toxins to under surveyed cellular contexts and emerging domains of regulation and is, therefore, a valuable resource to human health.

Automated summary

This study utilized a human-induced pluripotent stem cell-derived endothelial cell model to screen for an environmental toxin and examine its effect on the epitranscriptomic profile. Through multiomic analysis, the study identified specific RNAs affected by the toxin and conducted functional assays to characterize the phenotypic changes. The profiling of the epitranscriptome expands toxicological insights into under surveyed cellular contexts and emerging domains of regulation, providing a valuable resource for understanding human health.