ArticleCommunications biology2021
DNA methylation changes during long-term in vitro cell culture are caused by epigenetic drift.
Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 76 citations in OpenAlex.
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- Rescue of imprinted genes by epigenome editing in human cellular models of Prader-Willi syndrome.Nature communications · 2025Article
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- Cellular Models of Aging and Senescence.Cells · 2025Review
- Dynamic and reversible transcriptomic age shifts induced by COVID-19 in Korean whole blood.Aging · 2025Article
- Epigenetic editing at individual age-associated CpGs affects the genome-wide epigenetic aging landscape.Nature aging · 2025Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
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