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000294397 1001_ $$0P:(DE-He78)3648300630c504860c24d69ced68d908$$aBöhl, Elias$$b0$$eFirst author$$udkfz
000294397 245__ $$aAnalysis of population heterogeneity in CHO cells by genome-wide DNA methylation analysis and by multi-modal single-cell sequencing.
000294397 260__ $$aAmsterdam [u.a.]$$bElsevier Science$$c2024
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000294397 520__ $$aCHO 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.
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000294397 650_7 $$2Other$$aCHO cells
000294397 650_7 $$2Other$$aDNA methylation
000294397 650_7 $$2Other$$aEpigenetics
000294397 650_7 $$2Other$$aEvolution
000294397 650_7 $$2Other$$asingle-cell sequencing
000294397 650_7 $$2Other$$asubpopulations
000294397 7001_ $$0P:(DE-He78)e712dff472bccab611dd1641f262ea5a$$aRaddatz, Günter$$b1$$eFirst author$$udkfz
000294397 7001_ $$aRoy, Suki$$b2
000294397 7001_ $$aHuang, Lingzhi$$b3
000294397 7001_ $$aSandhu, Jasrene Kaur$$b4
000294397 7001_ $$aIgwe, Emeka Ignatius$$b5
000294397 7001_ $$0P:(DE-HGF)0$$aRodríguez-Paredes, Manuel$$b6
000294397 7001_ $$aBöhl, Florian$$b7
000294397 7001_ $$0P:(DE-He78)a8d53a8cdc716390a6cbacdead227143$$aLyko, Frank$$b8$$eLast author$$udkfz
000294397 773__ $$0PERI:(DE-600)2016476-2$$a10.1016/j.jbiotec.2024.10.012$$gp. S0168165624002852$$p72-79$$tJournal of biotechnology$$v396$$x0168-1656$$y2024
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