title: A signature of 12 microRNAs is robustly associated with growth rate in a variety of CHO cell lines.
abstract: As Chinese Hamster Ovary (CHO) cells are the cell line of choice for the production of human-like recombinant proteins, there is interest in genetic optimization of host cell lines to overcome certain limitations in their growth rate and protein secretion. At the same time, a detailed understanding of these processes could be used to advantage by identification of marker transcripts that characterize states of performance. In this context, microRNAs (miRNAs) that exhibit a robust correlation to the growth rate of CHO cells were determined by analyzing miRNA expression profiles in a comprehensive collection of 46 samples including CHO-K1, CHO-S and CHO-DUKXB11, which were adapted to various culture conditions, and analyzed in different growth stages using microarrays. By applying Spearman or Pearson correlation coefficient criteria of>|0.6|, miRNAs with high correlation to the overall growth, or growth rates observed in exponential, serum-free, and serum-free exponential phase were identified. An overlap of twelve miRNAs common for all sample sets was revealed, with nine positively and three negatively correlating miRNAs. The here identified panel of miRNAs can help to understand growth regulation in CHO cells and contains putative engineering targets as well as biomarkers for cell lines with advantageous growth characteristics.
authors.affiliation: Austrian Centre of Industrial Biotechnology, Austria; University of Natural Resources and Life Sciences, Austria. Electronic address: gerald.klanert@boku.ac.at.
authors.forename: Gerald
authors.initials: G
authors.lastname: Klanert
authors.affiliation: Austrian Centre of Industrial Biotechnology, Austria. Electronic address: vaibhav.jadhav@boku.ac.at.
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Jadhav
authors.affiliation: Austrian Centre of Industrial Biotechnology, Austria. Electronic address: vinoth.shanmukam@boku.ac.at.
authors.forename: Vinoth
authors.initials: V
authors.lastname: Shanmukam
authors.affiliation: Austrian Centre of Industrial Biotechnology, Austria. Electronic address: andreas.diendorfer@boku.ac.at.
authors.forename: Andreas
authors.initials: A
authors.lastname: Diendorfer
authors.affiliation: Graz University of Technology, Austria. Electronic address: michael.karbiener@medunigraz.at.
authors.forename: Michael
authors.initials: M
authors.lastname: Karbiener
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. Electronic address: marcel.scheideler@helmholtz-muenchen.de.
authors.forename: Marcel
authors.initials: M
authors.lastname: Scheideler
authors.affiliation: Austrian Centre of Industrial Biotechnology, Austria. Electronic address: juan.hernandez.bort@baxalta.com.
authors.forename: Juan Hernández
authors.initials: JH
authors.lastname: Bort
authors.affiliation: University of Natural Resources and Life Sciences, Austria. Electronic address: johannes.grillari@boku.ac.at.
authors.forename: Johannes
authors.initials: J
authors.lastname: Grillari
authors.affiliation: TAmirNA GmbH, Austria. Electronic address: matthias.hackl@tamirna.com.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hackl
authors.affiliation: Austrian Centre of Industrial Biotechnology, Austria; University of Natural Resources and Life Sciences, Austria. Electronic address: nicole.borth@boku.ac.at.
authors.forename: Nicole
authors.initials: N
authors.lastname: Borth
mesh_terms: D000818:Animals; D016466:CHO Cells / Q000378:metabolism* / Q000502:physiology*; D018929:Cell Culture Techniques / Q000379:methods*; D006224:Cricetinae; D003412:Cricetulus; D020869:Gene Expression Profiling; D035683:MicroRNAs / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011994:Recombinant Proteins
chemical_list: D035683:MicroRNAs; D011994:Recombinant Proteins
keywords: CHO; Correlation; Growth; Microarray; microRNA