ArticleGenome biology2015
Rapid reprogramming of epigenetic and transcriptional profiles in mammalian culture systems.
Article in Genome biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 168 citations in OpenAlex.
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- The oncogenic role of hypomethylated ZNF793 in gastric carcinoma: a focus on cell survival and stemness.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025Article
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- Using Callus as an Ex Vivo System for Chromatin Analysis.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Concomitant loss of TET2 and TET3 results in T cell expansion and genomic instability in mice.Communications biology · 2024Article
- Navigating Illumina DNA methylation data: biology versus technical artefacts.NAR genomics and bioinformatics · 2024Article
- Dysregulation of Transposon Transcription Profiles in Cancer Cells Resembles That of Embryonic Stem Cells.Current issues in molecular biology · 2024Article
- Primary Cell Culture as a Model System for Evolutionary Molecular Physiology.International journal of molecular sciences · 2024Review
- Kidney Disease Modeling with Organoids and Organs-on-Chips.Annual review of biomedical engineering · 2024Review
- Neuroinflammation-on-a-chip for multiple sclerosis research: a narrative review.Annals of medicine and surgery (2012) · 2024Review
- EpiDiP/NanoDiP: a versatile unsupervised machine learning edge computing platform for epigenomic tumour diagnostics.Acta neuropathologica communications · 2024Article
- Epigenetics of Genes Preferentially Expressed in Dissimilar Cell Populations: Myoblasts and Cerebellum.Epigenomes · 2024Article
- Epigenetic profiles guide improved CRISPR/Cas9-mediated gene knockout in human T cells.Nucleic acids research · 2024Article
- Review
- A conserved element in the first intron ofFrontiers in immunology · 2024Article
- Tissue explants as tools for studying the epigenetic modulation of the GH-IGF-I axis in farmed fish.Frontiers in physiology · 2024Article
- Bridging the gap: advancing cancer cell culture to reveal key metabolic targets.Frontiers in oncology · 2024Review
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundThe DNA methylation profiles of mammalian cell lines differ from those of the primary tissues from which they were derived, exhibiting increasing divergence from the in vivo methylation profile with extended time in culture. Few studies have directly examined the initial epigenetic and transcriptional consequences of adaptation of primary mammalian cells to culture, and the potential mechanisms through which this epigenetic dysregulation occurs is unknown.
resultsWe demonstrate that adaptation of mouse embryonic fibroblasts to cell culture results in a rapid reprogramming of epigenetic and transcriptional states. We observed global 5-hydroxymethylcytosine (5hmC) erasure within three days of culture initiation. Loss of genic 5hmC was independent of global 5-methylcytosine (5mC) levels and could be partially rescued by addition of vitamin C. Significantly, 5hmC loss was not linked to concomitant changes in transcription. Discrete promoter-specific gains of 5mC were also observed within seven days of culture initiation. Against this background of global 5hmC loss we identified a handful of developmentally important genes that maintained their 5hmC profile in culture, including the imprinted loci Gnas and H19. Similar outcomes were identified in the adaption of CD4(+) T cells to culture.
conclusionsWe report a dramatic and novel consequence of adaptation of mammalian cells to culture in which global loss of 5hmC occurs, suggesting rapid concomitant loss of methylcytosine dioxygenase activity. The observed epigenetic and transcriptional re-programming occurs much earlier than previously assumed, and has significant implications for the use of cell lines as faithful mimics of in vivo epigenetic and physiological processes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.