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@ARTICLE{Bhl:294397,
      author       = {E. Böhl$^*$ and G. Raddatz$^*$ and S. Roy and L. Huang and
                      J. K. Sandhu and E. I. Igwe and M. Rodríguez-Paredes$^*$
                      and F. Böhl and F. Lyko$^*$},
      title        = {{A}nalysis of population heterogeneity in {CHO} cells by
                      genome-wide {DNA} methylation analysis and by multi-modal
                      single-cell sequencing.},
      journal      = {Journal of biotechnology},
      volume       = {396},
      issn         = {0168-1656},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DKFZ-2024-02226},
      pages        = {72-79},
      year         = {2024},
      note         = {#EA:A130#LA:A130# / 2024 Oct 31:396:72-79 / DKFZ-ZMBH
                      Alliance},
      abstract     = {CHO cells are major hosts for the industrial production of
                      therapeutic proteins and their production stability is of
                      considerable economic significance. It is widely known that
                      CHO cells can rapidly acquire genetic alterations, which
                      affects their genetic homogeneity over time. However, the
                      role of non-genetic mechanisms, including epigenetic
                      mechanisms such as DNA methylation, remains poorly
                      understood. We have now used whole-genome bisulfite
                      sequencing to establish single-base methylation maps of
                      eight independent CHO cell lines. Our results identify CpG
                      islands and low-methylated regions as conserved elements
                      with dynamic DNA methylation. Interestingly, methylation
                      patterns were found to cluster clearly along the three main
                      branches of CHO evolution, with no directional changes over
                      short culture periods. Furthermore, multi-ome single-cell
                      sequencing of 9,833 nuclei from three independent cultures
                      revealed dynamic subpopulation structures characterized by
                      robust expression differences in pathways related to protein
                      production. Our findings thus provide novel insights into
                      the epigenetic landscape and heterogeneity of CHO cells and
                      support the development of epigenetic biomarkers that trace
                      the emergence of subpopulations in CHO cultures.},
      keywords     = {CHO cells (Other) / DNA methylation (Other) / Epigenetics
                      (Other) / Evolution (Other) / single-cell sequencing (Other)
                      / subpopulations (Other)},
      cin          = {A130},
      ddc          = {540},
      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:39488254},
      doi          = {10.1016/j.jbiotec.2024.10.012},
      url          = {https://inrepo02.dkfz.de/record/294397},
}