Comparative transcriptome analysis to unveil genes affecting recombinant protein productivity in mammalian cells

Joon Chong Yee, Ziomara P. Gerdtzen, Wei Shou Hu

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

Low temperature culture (33°C) has been shown to enhance the specific productivity of recombinant antibodies in Chinese hamster ovary (CHO) cells but did not affect antibody productivity in hybridoma (MAK) cells. We probed the transcriptional response of both cells undergoing temperature shift using cDNA microarrays. Among the orthologous gene probes, common trends in the expression changes between CHO and MAK are not prominent. Instead, many transcriptional changes were specific to only one cell line. Notably, oxidative phosphorylation and ribosomal genes were downregulated in MAK but not in CHO. Conversely, several protein trafficking genes and cytoskeleton elements were upregulated in CHO but remained unchanged in MAK. Interestingly, at 33°C, immunoglobulin heavy and light chain showed no significant changes in CHO, but the immunoglobulin light chain was downregulated in MAK. Overall, a clear distinction in the transcriptional response to low temperature was seen in the two cell lines. To further elucidate the set of genes responsible for increased antibody productivity, the expression data of low temperature cultures was compared to that of butyrate treatment which increased specific antibody productivity in both cell lines. Genes which are commonly differentially expressed under conditions that increased productivity are likely to reflect functional classes that are important in the productivity changes. This comparative transcriptome analysis suggests that vesicle trafficking, endocytosis and cytoskeletal elements are involved in increased specific antibody productivity.

Original languageEnglish (US)
Pages (from-to)246-263
Number of pages18
JournalBiotechnology and bioengineering
Volume102
Issue number1
DOIs
StatePublished - Jan 1 2009

Keywords

  • CDNA microarrays
  • CHO cells
  • Hybridoma
  • Mammalian cell culture
  • Transcriptome

Fingerprint

Dive into the research topics of 'Comparative transcriptome analysis to unveil genes affecting recombinant protein productivity in mammalian cells'. Together they form a unique fingerprint.

Cite this