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Improving product yield and quality has heavily relied on empirical characterization with limited insight into internal molecular dynamics. RNA\u2010seq offers a powerful alternative to understand intracellular responses to process changes through gene expression measurement. In this study, three RNA\u2010seq datasets across three CHO cell lines and four industrially relevant treatments were integrated to characterize the global transcriptome changes, construct a weighted gene co\u2010expression network, assess the impact on recombinant anti\u2010interleukin 8 (anti\u2010IL8) immunoglobulin heavy and light chain transcript abundance, and expression of glycosylation genes. Treatments included adaptation to serum\u2010free medium, low temperature, low pH, and low glucose concentration in the medium. The findings suggest upregulation of cholesterol biosynthesis is critical for serum\u2010free medium adaptation, and the rate\u2010limiting enzymes in the sterol regulatory element\u2010binding protein pathway (\n                    <jats:italic>Insig1<\/jats:italic>\n                    and\n                    <jats:italic>Srebf2<\/jats:italic>\n                    ) could be targeted to accelerate adaptation. Temperature\u2010induced cell cycle suppression was likely mediated by p53 activation, consistent with previous reports, with the p53\u2010targets,\n                    <jats:italic>Zmat3<\/jats:italic>\n                    and\n                    <jats:italic>Btg2<\/jats:italic>\n                    , identified as key hub genes. Conversely, glucose and pH were observed to have negligible impacts on the transcriptome. This study uniquely identifies novel genes mediating temperature\u2010induced cell cycle arrest, distinct glycosylation\u2010related gene responses impacting product quality, and new stable housekeeping genes for accurate gene expression normalization in CHO cells.\n                  <\/jats:p>","DOI":"10.1002\/biot.70055","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T03:30:03Z","timestamp":1751599803000},"source":"Crossref","is-referenced-by-count":7,"title":["Transcriptomic Insights Into Serum\u2010Free Medium Adaptation and Temperature Reduction in Chinese Hamster Ovary Cell Cultures"],"prefix":"10.1002","volume":"20","author":[{"given":"Benjamin F.","family":"Synoground","sequence":"first","affiliation":[{"name":"Department of Bioengineering Clemson University  Clemson South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogender","family":"Gowtham","sequence":"additional","affiliation":[{"name":"Department of 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