ArticlePloS one2018
Mild hypothermia upregulates myc and xbp1s expression and improves anti-TNFα production in CHO cells.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Using transcription and translation regulators to improve recombinant protein expression in CHO cells.Acta biochimica et biophysica Sinica · 2025Article
- Recent Advances in Engineering the Unfolded Protein Response in Recombinant Chinese Hamster Ovary Cell Lines.International journal of molecular sciences · 2025Review
- Bioprocess biomarker identification and diagnosis for industrial mAb production based on metabolic profiling and multivariate data analysis.Bioprocess and biosystems engineering · 2025Article
- Direct Consideration of Process History During Intensified Design of Experiments Planning Eases Interpretation of Mammalian Cell Culture Dynamics.Bioengineering (Basel, Switzerland) · 2025Article
- Improvement strategies for transient gene expression in mammalian cells.Applied microbiology and biotechnology · 2024Review
- Optimization of Culture Conditions to Improve Follicle-Stimulating Hormone Production by CHO-DG44 Cells in Serum-Free Medium.Iranian biomedical journal · 2024Article
- RNASeq highlights ATF6 pathway regulators for CHO cell engineering with different impacts of ATF6β and WFS1 knockdown on fed-batch production of IgGScientific reports · 2024Article
- Building blocks needed for mechanistic modeling of bioprocesses: A critical review based on protein production by CHO cells.Metabolic engineering communications · 2024Review
- Synergistic promotion of transient transgene expression in CHO cells by PDI/XBP-1s co-transfection and mild hypothermia.Bioprocess and biosystems engineering · 2024Article
- Recombinant therapeutic proteins degradation and overcoming strategies in CHO cells.Applied microbiology and biotechnology · 2024Review
- Housekeeping gene expression variability in differentiating and non-differentiating 3T3-L1 cells.Adipocyte · 2023Article
- Recombinant Human CD19 in CHO-K1 Cells: Glycosylation Patterns as a Quality Attribute of High Yield Processes.International journal of molecular sciences · 2023Article
- Engineering of Chinese hamster ovary cells for co-overexpressing MYC and XBP1s increased cell proliferation and recombinant EPO production.Scientific reports · 2023Article
- Adjustable Thermo-Responsive, Cell-Adhesive Tissue Engineering Scaffolds for Cell Stimulation through Periodic Changes in Culture Temperature.International journal of molecular sciences · 2022Article
- The potential of cold-shock promoters for the expression of recombinant proteins in microbes and mammalian cells.Journal, genetic engineering & biotechnology · 2022Review
- A comprehensive comparison of mixing and mass transfer in shake flasks and their relationship with MAb productivity of CHO cells.Bioprocess and biosystems engineering · 2022Article
- Article
- Dynamic Culture of Mesenchymal Stromal/Stem Cell Spheroids and Secretion of Paracrine Factors.Frontiers in bioengineering and biotechnology · 2022Review
- Factors Affecting the Expression of Recombinant Protein and Improvement Strategies in Chinese Hamster Ovary Cells.Frontiers in bioengineering and biotechnology · 2022Review
- Temperature Down-Shift Modifies Expression of UPR-/ERAD-Related Genes and Enhances Production of a Chimeric Fusion Protein in CHO Cells.Biotechnology journal · 2021Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chinese hamster ovary (CHO) cells are the most frequently used host for commercial production of therapeutic proteins. However, their low protein productivity in culture is the main hurdle to overcome. Mild hypothermia has been established as an effective strategy to enhance protein specific productivity, although the causes of such improvement still remain unclear. The self-regulation of global transcriptional regulatory factors, such as Myc and XBP1s, seems to be involved in increased the recombinant protein production at low temperature. This study evaluated the impact of low temperature in CHO cell cultures on myc and xbp1s expression and their effects on culture performance and cell metabolism. Two anti-TNFα producing CHO cell lines were selected considering two distinct phenotypes: i.e. maximum cell growth, (CN1) and maximum specific anti-TNFα production (CN2), and cultured at 37, 33 and 31°C in a batch system. Low temperature led to an increase in the cell viability, the expression of the recombinant anti-TNFα and the production of anti-TNFα both in CN1 and CN2. The higher production of anti-TNFα in CN2 was mainly associated with the large expression of anti-TNFα. Under mild hypothermia myc and xbp1s expression levels were directly correlated to the maximal viable cell density and the specific anti-TNFα productivity, respectively. Moreover, cells showed a simultaneous metabolic shift from production to consumption of lactate and from consumption to production of glutamine, which were exacerbated by reducing culture temperature and coincided with the increased anti-TNFα production. Our current results provide new insights of the regulation of myc and xbp1s in CHO cells at low temperature, and suggest that the presence and magnitude of the metabolic shift might be a relevant metabolic marker of productive cell line.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.