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首页> 外文期刊>Biotechnology Progress >Low Glucose Concentrations within Typical Industrial Operating Conditions Have Minimal Effect on the Transcriptome of Recombinant CHO Cells
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Low Glucose Concentrations within Typical Industrial Operating Conditions Have Minimal Effect on the Transcriptome of Recombinant CHO Cells

机译：典型工业操作条件下的低葡萄糖浓度对重组CHO细胞的转录组具有最小的影响

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Typically, mammalian cell culture medium contains high glucose concentrations that are analogous to diabetic levels in humans, suggesting that mammalian cells are cultivated in excessive glucose. Using RNA-Seq, this study characterized the Chinese hamster ovary (CHO) cell transcriptome under two glucose concentrations to assess the genetic effects associated with metabolic pathways, in addition to other global responses. The initial extracellular glucose concentrations used represented high (30 mM) and low (10 mM) glucose conditions, where at the time the transcriptomes were compared, the glucose concentrations were approximately 24 and 4.4 mM for the mid-exponential cultures, where 4.4 mM represents a common target concentration in the biopharmaceutical industry for controlled fed-batch cultures. A recombinant CHO cell line producing a monoclonal antibody was used, such that the impact on glycosylation genes could be evaluated. Relatively few genes were identified as being significantly different (FDR <= 0.01) between the high and low glucose conditions, for example, only 575 genes, and only 40 of these genes had 2-fold or greater differences. Gene expression differences for glycolysis, TCA cycle, and glycosylation-related reactions were minimal and unlikely to have biological significance. This transcriptome study indicates that low glucose concentrations in the culture medium are unlikely to cause any biologically significant or detrimental changes to CHO cells at the transcriptome level. Furthermore, it is well-known that maintaining low glucose concentrations in fed-batch cultures can reduce lactate production, which in turn improves process outcomes. Taken together, the transcriptome data supports the continued development of low glucose-based processes to control lactate. (C) 2017 American Institute of Chemical Engineers
机译：通常，哺乳动物细胞培养基含有与人类中类似糖尿病水平类似的高葡萄糖浓度，表明哺乳动物细胞在过度葡萄糖中培养。使用RNA-SEQ，该研究表征了两种葡萄糖浓度下的中国仓鼠卵巢（CHO）细胞转录组，以评估与代谢途径相关的遗传效应，以及其他全局反应。使用的初始细胞外葡萄糖浓度为高（30mm）和低（10mm）葡萄糖条件，在比较转录组时，葡萄糖浓度约为24和4.4mm，用于中指数培养，其中4.4mm代表用于受控批量生产的生物制药工业中的常见目标浓度。使用产生单克隆抗体的重组CHO细胞系，使得可以评估对糖基化基因的影响。鉴定相对较少的基因在高葡萄糖条件（例如，仅575个基因）之间具有显着不同（FDR <= 0.01），并且这些基因中只有40个具有2倍或更大的差异。基因表达对糖酵解，TCA循环和糖基化相关反应的差异最小，并且不太可能具有生物学意义。该转录组研究表明，培养基中的低葡萄糖浓度不太可能导致转录组水平对CHO细胞的任何生物学显着或有害的变化。此外，众所周知，维持融合培养物中的低葡萄糖浓度可以减少乳酸盐产生，这反过来改善了工艺结果。通过一起占据，转录组数据支持持续发展低葡萄糖的过程来控制乳酸。 （c）2017美国化学工程师研究所

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