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

Author:

Jousma Jordan1ORCID,Han Zhenbo1ORCID,Yan Gege1ORCID,Nukala Sarath Babu1ORCID,Kwon Youjeong1ORCID,Thi Le Hoai Huong2ORCID,Li Ya1,Ong Sang-Bing3456ORCID,Lee Won Hee2ORCID,Ong Sang-Ging137ORCID

Affiliation:

1. Department of Pharmacology & Regenerative Medicine, The University of Illinois College of Medicine, 909 S Wolcott Ave, COMRB 4100, Chicago, IL 60612, USA

2. Department of Basic Medical Sciences, University of Arizona College of Medicine, ABC-1 Building, 425 North 5th Street, Phoenix, AZ 85004, USA

3. Department of Medicine & Therapeutics, Faculty of Medicine, Chinese University of Hong Kong (CUHK), Hong Kong SAR, China

4. Centre for Cardiovascular Genomics & Medicine (CCGM), Lui Che Woo Institute of Innovative Medicine, CUHK, Hong Kong SAR, China

5. Hong Kong Hub of Paediatric Excellence (HK HOPE), Hong Kong Children's Hospital (HKCH), Kowloon Bay, Hong Kong SAR, China

6. Kunming Institute of Zoology – The Chinese University of Hong Kong (KIZ-CUHK) Joint Laboratory of Bioresources & Molecular Research of Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223 Yunnan, China

7. Division of Cardiology, Department of Medicine, The University of Illinois College of Medicine, 909 S Wolcott Ave, COMRB 4100, Chicago, IL 60612, USA

Abstract

Background: This study aimed to characterize the N6-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 N6-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.

Funder

American Heart Association

National Heart, Lung, and Blood Institute

Publisher

Future Medicine Ltd

Subject

Cancer Research,Genetics

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