ArticlePloS one2016
Effect of Temperature Downshift on the Transcriptomic Responses of Chinese Hamster Ovary Cells Using Recombinant Human Tissue Plasminogen Activator Production Culture.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 63 citations in OpenAlex.
- Improvement of protein purity in etanercept production through process optimization in recombinant CHO cell-based transient gene expression system.Bioprocess and biosystems engineering · 2026Article
- Proteomic and Ubiquitinated Proteome Insights Into ER Stress Responses in Chinese Hamster Ovary Cells Under Mild Hypothermic Conditions.Biotechnology and bioengineering · 2026Article
- 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
- Transcriptomic Insights Into Serum-Free Medium Adaptation and Temperature Reduction in Chinese Hamster Ovary Cell Cultures.Biotechnology journal · 2025Article
- 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
- Aggregation of human osteoblasts unlocks self-reliant differentiation and constitutes a microenvironment for 3D-co-cultivation with other bone marrow cells.Scientific reports · 2024Article
- Engineering of Chinese hamster ovary cells for co-overexpressing MYC and XBP1s increased cell proliferation and recombinant EPO production.Scientific reports · 2023Article
- Comparative study of commercial media to improve GMP manufacturing of recombinant human interferon β-1a by CHO cells in perfusion bioreactor.Cytotechnology · 2022Article
- Hyperosmolality in CHO cell culture: effects on the proteome.Applied microbiology and biotechnology · 2022Article
- Dynamic Culture of Mesenchymal Stromal/Stem Cell Spheroids and Secretion of Paracrine Factors.Frontiers in bioengineering and biotechnology · 2022Review
- Article
- Enhancement of Transgene Expression by Mild Hypothermia Is Promoter Dependent in HEK293 Cells.Life (Basel, Switzerland) · 2021Article
- Article
- Temperature Down-Shift Modifies Expression of UPR-/ERAD-Related Genes and Enhances Production of a Chimeric Fusion Protein in CHO Cells.Biotechnology journal · 2021Article
- Decoupling Growth and Protein Production in CHO Cells: A Targeted Approach.Frontiers in bioengineering and biotechnology · 2021Article
- CHOmics: A web-based tool for multi-omics data analysis and interactive visualization in CHO cell lines.PLoS computational biology · 2020Article
- A temperature-dependent conformational shift in p38α MAPK substrate-binding region associated with changes in substrate phosphorylation profile.The Journal of biological chemistry · 2019Article
- Therapeutic Fc fusion protein misfolding: A three-phasic cultivation experimental design.PloS one · 2019Article
- Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recombinant proteins are widely used as biopharmaceuticals, but their production by mammalian cell culture is expensive. Hence, improvement of bioprocess productivity is greatly needed. A temperature downshift (TDS) from 37°C to 28-34°C is an effective strategy to expand the productive life period of cells and increase their productivity (qp). Here, TDS in Chinese hamster ovary (CHO) cell cultures, initially grown at 37°C and switched to 30°C during the exponential growth phase, resulted in a 1.6-fold increase in the qp of recombinant human tissue plasminogen activator (rh-tPA). The transcriptomic response using next-generation sequencing (NGS) was assessed to characterize the cellular behavior associated with TDS. A total of 416 (q > 0.8) and 3,472 (q > 0.9) differentially expressed transcripts, with more than a 1.6-fold change at 24 and 48 h post TDS, respectively, were observed in cultures with TDS compared to those at constant 37°C. In agreement with the extended cell survival resulting from TDS, transcripts related to cell growth arrest that controlled cell proliferation without the activation of the DNA damage response, were differentially expressed. Most upregulated genes were related to energy metabolism in mitochondria, mitochondrial biogenesis, central metabolism, and avoidance of apoptotic cell death. The gene coding for rh-tPA was not differentially expressed, but fluctuations were detected in the transcripts encoding proteins involved in the secretory machinery, particularly in glycosylation. Through NGS the dynamic processes caused by TDS were assessed in this biological system.
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