Global structure and determinants of transcriptomic adaptation in CHO cells

Transcriptomic adaptation plays a central role in the phenotypic plasticity of Chinese hamster ovary (CHO) cells. While various gene expression studies have provided insights into condition-specific responses, a comprehensive, systems-level understanding of how CHO cell transcriptomes dynamically adapt across diverse experimental contexts remains limited. Here, we present a large-scale investigation of more than 600 RNA-seq samples across diverse cell lines, culture conditions and experimental designs to systematically dissect stable and adaptive components of the transcriptome. We consolidate robust expression variance measures across datasets to identify a global axis of gene expression variability that summarizes transcriptional adaptation across common experimental settings. Functional enrichment analyses reveal that highly variable genes are associated with stress response mechanisms, extracellular interactions, signaling and apoptosis, whereas low-variability genes are enriched for RNA metabolism, intracellular transport and basal transcription. Analyses of regulatory features of genes with different variabilities show distinct promoter architectures and epigenetic signatures consistent with dynamic transcriptional control. Beyond this global axis of transcriptional adaptation, we capture context-specific transcriptional programs linked to experimental designs, including temperature downshift and growth phase transitions. Together, these findings delineate a common, low-variability transcriptional core alongside a variable, flexible layer that enables adaptive responses. Our work advances the understanding of transcriptional robustness and plasticity in CHO cells, provides practical guidance for reference gene selection and may offer potential for rational engineering for more robust cell lines.