PMID- 30024106
OWN - NLM
STAT- MEDLINE
DCOM- 20190614
LR  - 20211204
IS  - 1860-7314 (Electronic)
IS  - 1860-6768 (Linking)
VI  - 14
IP  - 3
DP  - 2019 Mar
TI  - Transcriptome Analysis of CHO Cell Size Increase During a Fed-Batch Process.
PG  - e1800156
LID - 10.1002/biot.201800156 [doi]
AB  - 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 G(0) /G(1) 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.
CI  - (c) 2018 The Authors. Biotechnology Journal Published by Wiley-VCH Verlag GmbH & 
      Co. KGaA.
FAU - Pan, Xiao
AU  - Pan X
AD  - Bioprocess Engineering, Wageningen University and Research, PO Box 16, 6700 AA, 
      Wageningen, The Netherlands.
FAU - Alsayyari, Abdulaziz A
AU  - Alsayyari AA
AD  - Bioprocess Engineering, Wageningen University and Research, PO Box 16, 6700 AA, 
      Wageningen, The Netherlands.
FAU - Dalm, Ciska
AU  - Dalm C
AD  - Upstream Process Development, Synthon Biopharmaceuticals BV, PO Box 7071, 6503 
      GN, Nijmegen, The Netherlands.
FAU - Hageman, Jos A
AU  - Hageman JA
AD  - Biometris, Wageningen University and Research, P.O. Box 16, 6700 AA, Wageningen, 
      The Netherlands.
FAU - Wijffels, Rene H
AU  - Wijffels RH
AD  - Bioprocess Engineering, Wageningen University and Research, PO Box 16, 6700 AA, 
      Wageningen, The Netherlands.
AD  - Faculty of Biosciences and Aquaculture, Nord University, N-8049, Bodo, Norway.
FAU - Martens, Dirk E
AU  - Martens DE
AD  - Bioprocess Engineering, Wageningen University and Research, PO Box 16, 6700 AA, 
      Wageningen, The Netherlands.
LA  - eng
GR  - 2011-020586/GO EFRO 2007-2013/
PT  - Journal Article
DEP - 20180730
PL  - Germany
TA  - Biotechnol J
JT  - Biotechnology journal
JID - 101265833
RN  - 0 (Cyclins)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
SB  - IM
MH  - Animals
MH  - CHO Cells
MH  - Cell Culture Techniques/methods
MH  - Cell Cycle Checkpoints/genetics
MH  - Cell Proliferation/genetics
MH  - Cricetulus
MH  - Cyclin-Dependent Kinases/genetics
MH  - Cyclins/genetics
MH  - G1 Phase/genetics
MH  - Gene Expression/genetics
MH  - Gene Expression Profiling/methods
MH  - Resting Phase, Cell Cycle/genetics
MH  - TOR Serine-Threonine Kinases/genetics
MH  - Transcription, Genetic/genetics
MH  - Transcriptome/*genetics
MH  - Up-Regulation/genetics
OTO - NOTNLM
OT  - CHO cell culture
OT  - cell cycle
OT  - cell size increase
OT  - mAb production
OT  - mTOR
OT  - transcriptome analysis
EDAT- 2018/07/20 06:00
MHDA- 2019/06/15 06:00
CRDT- 2018/07/20 06:00
PHST- 2018/03/21 00:00 [received]
PHST- 2018/07/11 00:00 [revised]
PHST- 2018/07/20 06:00 [pubmed]
PHST- 2019/06/15 06:00 [medline]
PHST- 2018/07/20 06:00 [entrez]
AID - 10.1002/biot.201800156 [doi]
PST - ppublish
SO  - Biotechnol J. 2019 Mar;14(3):e1800156. doi: 10.1002/biot.201800156. Epub 2018 Jul 
      30.