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@ARTICLE{Roy:309697,
      author       = {S. Roy and J. K. Sandhu and L. Huang and A. Wong and G. X.
                      Wan and F. Lyko$^*$ and E. I. Igwe and F. Böhl},
      title        = {{W}hole-genome {DNA} methylation analysis of {C}hinese
                      hamster ovary cells undergoing media adaptation.},
      journal      = {Frontiers in Bioengineering and Biotechnology},
      volume       = {14},
      issn         = {2296-4185},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2026-00310},
      pages        = {1716758},
      year         = {2026},
      abstract     = {Chinese Hamster Ovary (CHO) cells are widely used for the
                      production of recombinant therapeutics due to their ability
                      to carry out human-like post-translational modifications.
                      Media adaptation represents a key step in large-scale
                      production to ensure optimal safety and cost efficiency. As
                      DNA methylation is a central epigenetic mechanism underlying
                      adaptive modulation of gene expression, we report here, for
                      the first time, the use of high-coverage whole-genome
                      bisulfite sequencing to generate single-base-resolution maps
                      of CHO cells at different phases of growth in a fed-batch
                      culture and undergoing media adaptation across four
                      different media.A CHO cell line was adapted to four
                      commercially available media, and their growth rates and
                      productivity were compared with those obtained using the
                      control medium in a 7-day batch culture. This approach
                      resulted in the generation of n = 57 high-quality
                      whole-genome DNA methylation datasets, which were subjected
                      to differential DNA methylation and gene association
                      analyses. In addition, we developed a novel DNA methylation
                      array comprising more than 63,000 CpG methylation sites
                      across the CHO genome, enabling streamlined and efficient
                      DNA methylation profiling of CHO cells.Analysis of n = 57
                      high-quality DNA methylation datasets revealed altered DNA
                      methylation patterns across different phases of growth in a
                      fed-batch culture and in response to distinct media
                      adaptations. Specifically, adaptation to four different
                      media resulted in highly specific methylation changes that
                      were associated with distinct functional outcomes, including
                      protein productivity. Finally, the customized DNA
                      methylation microarray platform was used to validate all
                      media adaptation-dependent epigenetic changes identified by
                      whole-genome bisulfite sequencing (WGBS).These findings
                      identify and characterize dynamic DNA methylation changes
                      occurring during media adaptation and support their
                      potential use as predictive indicators of CHO cell
                      phenotypic changes in response to a dynamic culture
                      environment. Furthermore, this work represents a valuable
                      resource for the development of DNA methylation-based
                      biomarkers for the optimization of CHO cell culture.},
      keywords     = {Chinese hamster ovary (CHO) cells (Other) / DNA methylation
                      (Other) / epigenetics (Other) / media adaptation (Other) /
                      whole-genome bisulfite sequencing (WGBS), DNA methylation
                      array (Other)},
      cin          = {A130},
      ddc          = {570},
      cid          = {I:(DE-He78)A130-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41647358},
      pmc          = {pmc:PMC12868252},
      doi          = {10.3389/fbioe.2026.1716758},
      url          = {https://inrepo02.dkfz.de/record/309697},
}