Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 549156
Title Transcriptome Analysis of CHO Cell Size Increase During a Fed-Batch Process
Author(s) Pan, Xiao; Alsayyari, Abdulaziz A.; Dalm, Ciska; Hageman, Jos A.; Wijffels, René H.; Martens, Dirk E.
Source Biotechnology Journal 14 (2019)3. - ISSN 1860-6768
Department(s) Bioprocess Engineering
Mathematical and Statistical Methods - Biometris
Publication type Refereed Article in a scientific journal
Publication year 2019
Keyword(s) cell cycle - cell size increase - CHO cell culture - mAb production - mTOR - transcriptome analysis
Abstract In a Chinese Hamster Ovary (CHO) cell fed-batch process, arrest of cell proliferation and an almost threefold increase in cell size occurred, which is associated with an increase in cell-specific productivity. In this study, transcriptome analysis is performed to identify the molecular mechanisms associated with this. Cell cycle analysis reveals that the cells are arrested mainly in the G0/G1 phase. The cell cycle arrest is associated with significant up-regulation of cyclin-dependent kinases inhibitors (CDKNs) and down-regulation of cyclin-dependent kinases (CDKs) and cyclins. During the cell size increase phase, the gene expression of the upstream pathways of mechanistic target of rapamycin (mTOR), which is related to the extracellular growth factor, cytokine, and amino acid conditions, shows a strongly synchronized pattern to promote the mTOR activity. The downstream genes of mTOR also show a synchronized pattern to stimulate protein translation and lipid synthesis. The results demonstrate that cell cycle inhibition and stimulated mTOR activity at the transcriptome level are related to CHO cell size increase. The cell size increase is related to the extracellular nutrient conditions through a number of cascade pathways, indicating that by rational design of media and feeds, CHO cell size can be manipulated during culture processes, which may further improve cell growth and specific productivity.
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