ArticleScientific reports2018
Disruption of mesoderm formation during cardiac differentiation due to developmental exposure to 13-cis-retinoic acid.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Deciphering epigenetic regulation in cardiac developmental toxicity: Mechanisms and implications (Review).Molecular medicine reports · 2026Review
- An RNA polymerase III tissue and tumor atlas uncovers context-specific activities linked to 3D epigenome regulatory mechanisms.bioRxiv : the preprint server for biology · 2025Article
- Maturation of human induced pluripotent stem cell-derived cardiomyocytes promoted by Brachyury priming.Scientific reports · 2025Article
- Standardization and optimization of the hiPSC-based PluriLum assay for detection of embryonic and developmental toxicants.Archives of toxicology · 2024Article
- Investigating the applicability domain of the hiPSC-based PluriLum assay: an embryotoxicity assessment of chemicals and drugs.Archives of toxicology · 2024Article
- Review
- Developmental Toxicity Studies: The Path towards Humanized 3D Stem Cell-Based Models.International journal of molecular sciences · 2023Review
- Ectopic expression of SARS-CoV-2 S and ORF-9B proteins alters metabolic profiles and impairs contractile function in cardiomyocytes.Frontiers in cell and developmental biology · 2023Article
- Cardiac Development in the Presence of Cadmium: AnEnvironmental health perspectives · 2022Article
- Article
- Engineering spatial-organized cardiac organoids for developmental toxicity testing.Stem cell reports · 2021Article
- In situ differentiation of human-induced pluripotent stem cells into functional cardiomyocytes on a coaxial PCL-gelatin nanofibrous scaffold.Materials science & engineering. C, Materials for biological applications · 2021Article
- Heart Enhancers: Development and Disease Control at a Distance.Frontiers in genetics · 2021Review
- A novel human pluripotent stem cell-based assay to predict developmental toxicity.Archives of toxicology · 2020Article
- Reiterative Mechanisms of Retinoic Acid Signaling during Vertebrate Heart Development.Journal of developmental biology · 2019Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
13-cis-retinoic acid (isotretinoin, INN) is an oral pharmaceutical drug used for the treatment of skin acne, and is also a known teratogen. In this study, the molecular mechanisms underlying INN-induced developmental toxicity during early cardiac differentiation were investigated using both human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs). Pre-exposure of hiPSCs and hESCs to a sublethal concentration of INN did not influence cell proliferation and pluripotency. However, mesodermal differentiation was disrupted when INN was included in the medium during differentiation. Transcriptomic profiling by RNA-seq revealed that INN exposure leads to aberrant expression of genes involved in several signaling pathways that control early mesoderm differentiation, such as TGF-beta signaling. In addition, genome-wide chromatin accessibility profiling by ATAC-seq suggested that INN-exposure leads to enhanced DNA-binding of specific transcription factors (TFs), including HNF1B, SOX10 and NFIC, often in close spatial proximity to genes that are dysregulated in response to INN treatment. Altogether, these results identify potential molecular mechanisms underlying INN-induced perturbation during mesodermal differentiation in the context of cardiac development. This study further highlights the utility of human stem cells as an alternative system for investigating congenital diseases of newborns that arise as a result of maternal drug exposure during pregnancy.
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