Identifying key signatures of high productivity from transcriptome and proteome profiles of CHO cells

Abstract

In an effort to identify key cellular processes that confer high recombinant protein productivity, we combined transcriptome and proteome analysis to evaluate differentially expressed genes and proteins in chinese hamster ovary (CHO) cells producing high and low levels of dhfr-GFP fusion recombinant protein. A proprietary 7559-element CHO cDNA microarray and iTRAQ LC-MS were used to analyze transcription patterns and protein levels respectively. Identified genes and proteins are not correspondent, but results from both datasets concur based on functional categorization. High producing cells have increased energy generation through lipid and carbohydrate metabolism, and more mitochondria; decreased cell proliferation and reduced apoptosis; increased activity in processes related to protein biosynthesis such as transcription, translation, protein folding and protein degradation; and reduced response in ER and oxidative stress. This study also demonstrates that integrating genomics and proteomics is an effective approach to monitor transcriptional and post-transcriptional events of mammalian cells in culture.