title: Transcriptomic analysis of clonal growth rate variation during CHO cell line development.
abstract: The selection of clones displaying a high rate of cell growth is an essential component of Chinese hamster ovary (CHO) cell line development. In recent years various "omics" technologies have been utilised to understand the mechanisms underlying bioprocess phenotypes. In this study, gene expression analysis using a CHO-specific microarray was conducted for a panel of CHO-K1 MAb-secreting cell lines spanning a range of growth rates that were derived from a single cell line development project. In-silico functional analysis of the resulting transcriptomic data revealed the overrepresentation of biological processes such as cell cycle and translation within those genes upregulated during fast growth, while genes associated with cellular homeostasis were downregulated. Using differential expression and correlation analysis we identified a high priority group of 416 transcripts (190 upregulated; 226 downregulated) associated with growth rate. Expression changes of eight of these genes were independently confirmed by qPCR. Finally, we demonstrate the enrichment of predicted mRNA targets of miR17-92, a microRNA (miRNA) cluster known to be upregulated during rapid proliferation, within downregulated transcripts.
authors: National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland.
authors: Padraig
authors: P
authors: Doolan
authors: Colin
authors: C
authors: Clarke
authors: Paula
authors: P
authors: Kinsella
authors: Laura
authors: L
authors: Breen
authors: Paula
authors: P
authors: Meleady
authors: Mark
authors: M
authors: Leonard
authors: Lin
authors: L
authors: Zhang
authors: Martin
authors: M
authors: Clynes
authors: Sinead T
authors: ST
authors: Aherne
authors: Niall
authors: N
authors: Barron
mesh_terms: D000818:Animals; D016466:CHO Cells; D002453:Cell Cycle / Q000235:genetics*; D049109:Cell Proliferation; D002470:Cell Survival; D006224:Cricetinae; D003412:Cricetulus; D015536:Down-Regulation; D020869:Gene Expression Profiling; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs