Franzen, Julia ORCID: 0000-0002-2459-5841, Georgomanolis, Theodoros, Selich, Anton, Kuo, Chao-Chung ORCID: 0000-0001-8879-4754, Stoeger, Reinhard, Brant, Lilija, Mulabdic, Melita Sara, Fernandez-Rebollo, Eduardo, Grezella, Clara, Ostrowska, Alina, Begemann, Matthias, Nikolic, Milos, Rath, Bjoern, Ho, Anthony D., Rothe, Michael, Schambach, Axel, Papantonis, Argyris and Wagner, Wolfgang (2021). DNA methylation changes during long-term in vitro cell culture are caused by epigenetic drift. Commun. Biol., 4 (1). BERLIN: NATURE RESEARCH. ISSN 2399-3642

Full text not available from this repository.

Abstract

Culture expansion of primary cells evokes highly reproducible DNA methylation (DNAm) changes. We have identified CG dinucleotides (CpGs) that become continuously hyper- or hypomethylated during long-term culture of mesenchymal stem cells (MSCs) and other cell types. Bisulfite barcoded amplicon sequencing (BBA-seq) demonstrated that DNAm patterns of neighboring CpGs become more complex without evidence of continuous pattern development and without association to oligoclonal subpopulations. Circularized chromatin conformation capture (4C) revealed reproducible changes in nuclear organization between early and late passages, while there was no enriched interaction with other genomic regions that also harbor culture-associated DNAm changes. Chromatin immunoprecipitation of CTCF did not show significant differences during long-term culture of MSCs, however culture-associated hypermethylation was enriched at CTCF binding sites and hypomethylated CpGs were devoid of CTCF. Taken together, our results support the notion that DNAm changes during culture-expansion are not directly regulated by a targeted mechanism but rather resemble epigenetic drift. Julia Franzen et al. investigate if changes in DNA methylation at specific genetic loci during cell culture expansion are due to a specific mechanism or gradual deregulation of an epigenetic state. Their results suggest that changes in CpG methylation are due to indirect epigenetic drift, rather than a consequence of targeting by DNA methyltransferases.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Franzen, JuliaUNSPECIFIEDorcid.org/0000-0002-2459-5841UNSPECIFIED
Georgomanolis, TheodorosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Selich, AntonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuo, Chao-ChungUNSPECIFIEDorcid.org/0000-0001-8879-4754UNSPECIFIED
Stoeger, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brant, LilijaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mulabdic, Melita SaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fernandez-Rebollo, EduardoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grezella, ClaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ostrowska, AlinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Begemann, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nikolic, MilosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rath, BjoernUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ho, Anthony D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rothe, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schambach, AxelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Papantonis, ArgyrisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-595051
DOI: 10.1038/s42003-021-02116-y
Journal or Publication Title: Commun. Biol.
Volume: 4
Number: 1
Date: 2021
Publisher: NATURE RESEARCH
Place of Publication: BERLIN
ISSN: 2399-3642
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MESENCHYMAL STROMAL CELLS; PLURIPOTENT STEM-CELLS; SENESCENCE; HEMIMETHYLATION; REORGANIZATION; ORGANIZATION; MAINTENANCE; PLASTICITY; EXPANSION; PATTERNSMultiple languages
Biology; Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59505

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item