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  DMSO induces drastic changes in human cellular processes and epigenetic landscape in vitro

Verheijen, M., Lienhard, M., Schrooders, Y., Clayton, O., Nudischer, R., Boerno, S. T., et al. (2019). DMSO induces drastic changes in human cellular processes and epigenetic landscape in vitro. Scientific Reports, 9(9): 4641. doi:10.1038/s41598-019-40660-0.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0003-5172-1 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-5173-0
Genre: Journal Article

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Verheijen, M., Author
Lienhard, M.1, Author              
Schrooders, Y., Author
Clayton, O., Author
Nudischer, R., Author
Boerno, S. T.2, Author              
Timmermann, B.2, Author              
Selevsek, N., Author
Schlapbach, R., Author
Gmuender, H., Author
Gotta, S., Author
Geraedts, J., Author
Herwig, R.1, Author              
Kleinjans, J., Author
Caiment, F., Author
Affiliations:
1Bioinformatics (Ralf Herwig), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2385701              
2Sequencing (Head: Bernd Timmermann), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479670              

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 Abstract: Though clinical trials for medical applications of dimethyl sulfoxide (DMSO) reported toxicity in the 1960s, later, the FDA classified DMSO in the safest solvent category. DMSO became widely used in many biomedical fields and biological effects were overlooked. Meanwhile, biomedical science has evolved towards sensitive high-throughput techniques and new research areas, including epigenomics and microRNAs. Considering its wide use, especially for cryopreservation and in vitro assays, we evaluated biological effect of DMSO using these technological innovations. We exposed 3D cardiac and hepatic microtissues to medium with or without 0.1% DMSO and analyzed the transcriptome, proteome and DNA methylation profiles. In both tissue types, transcriptome analysis detected >2000 differentially expressed genes affecting similar biological processes, thereby indicating consistent cross-organ actions of DMSO. Furthermore, microRNA analysis revealed large-scale deregulations of cardiac microRNAs and smaller, though still massive, effects in hepatic microtissues. Genome-wide methylation patterns also revealed tissue-specificity. While hepatic microtissues demonstrated non-significant changes, findings from cardiac microtissues suggested disruption of DNA methylation mechanisms leading to genome-wide changes. The extreme changes in microRNAs and alterations in the epigenetic landscape indicate that DMSO is not inert. Its use should be reconsidered, especially for cryopreservation of embryos and oocytes, since it may impact embryonic development.

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Language(s): eng - English
 Dates: 2019-02-202019-03-15
 Publication Status: Published online
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 Identifiers: DOI: 10.1038/s41598-019-40660-0
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Title: Scientific Reports
  Abbreviation : Sci. Rep.
Source Genre: Journal
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Publ. Info: London, UK : Nature Publishing Group
Pages: - Volume / Issue: 9 (9) Sequence Number: 4641 Start / End Page: - Identifier: ISSN: 2045-2322
CoNE: https://pure.mpg.de/cone/journals/resource/2045-2322