Long- and short-term genomic and epigenetic changes in Chinese Hamster Ovary cells. CHO_genomic_epigenomic_changes

One of the most striking characteristics of CHO cells is their adaptability, enabling the efficient production of proteins and growth under a variety of culture conditions and bioprocess types. The backside is their genomic and phenotypic instablility which may lead to process variations, loss of productivity or changes in product quality. Potential causes include (1) chromosomal rearrangements found in any immortalised or cancer cell line; (2) variations in chromosome numbers; (3) SNPs or indels as observed in those cell lines sequenced so far; (4) epigenetic regulation of gene expression. To understand the relative contribution of these, 6 full genome sequences and 7 methylomes of related cell lines were analysed at the level of SNPs, indels, structural variants and changes in methylation pattern. In addition, histone modifications at several timepoints of a batch culture and the full genome DNA methylation pattern during exponential and stationary growth are presented. These datasets will enable a better understanding of epigenetic regulation in CHO cells and open the door for improved control and manipulation of gene expression during industrial bioprocesses.