An Online Compendium of CHO RNA‐Seq Data Allows Identification of CHO Cell Line‐Specific Transcriptomic Signatures

Abstract

Chinese hamster ovary (CHO) cell lines can fold, assemble, and modify proteins post-translationally to produce human-like proteins; as a consequence, it is the single most common expression systems for industrial production of recombinant therapeutic proteins. A thorough knowledge of cultivation conditions of different CHO cell lines has been developed over the last decade, but comprehending gene or pathway-specific distinctions between CHO cell lines at transcriptome level remains a challenge. To address these challenges, a compendium of 23 RNA-Seq studies from public and in-house data on CHO cell lines, i.e., CHO-S, CHO-K1, and DG44 is compiled. Significantly differentially expressed (DE) genes particularly related to subcellular structure and macromolecular categories are used to identify differences between the cell lines. A R-based web application is developed specifically for CHO cell lines to further visualize expression values across different cell lines, and make available the normalized full CHO data set graphically as a CHO research community resource. This study quantitatively categorizes CHO cell lines based on patterns at transcriptomic level and detects gene and pathway specific key distinctions among sibling cell lines. Studies such as this can be used to select desired characteristics across various CHO cell lines. Furthermore, the availability of the data as an internet-based application can be applied to broad range of CHO engineering applications.

A cross-species whole genome siRNA screen in suspension-cultured Chinese hamster ovary cells identifies novel engineering targets

“…Vice-versa, a gene that impairs high production rate may be successfully knocked down in a cell line that expresses it at high level, while little effects are observed in a cell line that has already decreased expression. Thus cell line engineering approaches are likely to be dependent of the overall transcriptome context 59,60 and may in the future have to be “personalized” to the specific needs of a given cell line. This also implies that such screens should routinely be run with more than one model cell line to ensure identification of all relevant genes.…”

Transcriptome Analysis of CHO Cell Size Increase During a Fed-Batch Process

“…The metabolic changes associated with the cell size increase were studied in detail using flux balance analysis; however, the cause and molecular mechanisms for the cell size increase remained unclear. Transcriptome analysis has been used as a powerful tool to better understand the physiology of CHO cell lines . The aim of the present study is to obtain more insights into the cause and the molecular mechanisms underlying the CHO cell size increase using transcriptome analysis.…”

Genetic and Epigenetic Variation across Genes Involved in Energy Metabolism and Mitochondria of Chinese Hamster Ovary Cell Lines

“…Another in‐frame insertion (NW_006879460 716861: >AGA) within the acyl‐CoA synthetase (ACSL4) gene was found to be coexisting in CHO‐K1 1D9‐MCB and the recombinant protein producing cell line (C0101) derived from suspension grown cells (CHO‐S). As ACSL4 is a peroxisomal acyl‐CoA synthetase, which is involved in essential lipid metabolic functions and could be associated with vesicular transport, it could also be an interesting candidate to investigate for enhancing protein secretion and transport …”

“…As ACSL4 is a peroxisomal acyl-CoA synthetase, which is involved in essential lipid metabolic functions [65] and could be associated with vesicular transport, it could also be an interesting candidate to investigate for enhancing protein secretion and transport. [66]…”