Comprehensive genome and epigenome characterization of CHO cells in response to evolutionary pressures and over time

Julia Feichtinger, Inmaculada Hernández, Christoph Fischer, Michael Hanscho, Norbert Auer, Matthias Hackl, Vaibhav Jadhav, Martina Baumann, Peter M Krempl, Christian Schmidl, Matthias Farlik, Michael Schuster, Angelika Merkel, Andreas Sommer, Simon Heath, Daniel Rico, Christoph Bock, Gerhard G Thallinger, Nicole Borth

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The most striking characteristic of CHO cells is their adaptability, which enables efficient production of proteins as well as growth under a variety of culture conditions, but also results in genomic and phenotypic instability. To investigate the relative contribution of genomic and epigenetic modifications towards phenotype evolution, comprehensive genome and epigenome data are presented for six related CHO cell lines, both in response to perturbations (different culture conditions and media as well as selection of a specific phenotype with increased transient productivity) and in steady state (prolonged time in culture under constant conditions). Clear transitions were observed in DNA-methylation patterns upon each perturbation, while few changes occurred over time under constant conditions. Only minor DNA-methylation changes were observed between exponential and stationary growth phase; however, throughout a batch culture the histone modification pattern underwent continuous adaptation. Variation in genome sequence between the six cell lines on the level of SNPs, InDels, and structural variants is high, both upon perturbation and under constant conditions over time. The here presented comprehensive resource may open the door to improved control and manipulation of gene expression during industrial bioprocesses based on epigenetic mechanisms. Biotechnol. Bioeng. 2016;113: 2241-2253. © 2016 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.

Original languageEnglish
Pages (from-to)2241-53
Number of pages13
JournalBiotechnology and Bioengineering
Volume113
Issue number10
DOIs
Publication statusPublished - Oct 2016

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CHO Cells
Genes
Genome
DNA Methylation
Pressure
Epigenomics
Biotechnology
Histone Code
Gene expression
Histones
Phenotype
Cell Line
Bioengineering
Batch Cell Culture Techniques
Genomic Instability
Productivity
Cells
Growth
Proteins
Single Nucleotide Polymorphism

Keywords

  • Journal Article

Cite this

Comprehensive genome and epigenome characterization of CHO cells in response to evolutionary pressures and over time. / Feichtinger, Julia; Hernández, Inmaculada; Fischer, Christoph; Hanscho, Michael; Auer, Norbert; Hackl, Matthias; Jadhav, Vaibhav; Baumann, Martina; Krempl, Peter M; Schmidl, Christian; Farlik, Matthias; Schuster, Michael; Merkel, Angelika; Sommer, Andreas; Heath, Simon; Rico, Daniel; Bock, Christoph; Thallinger, Gerhard G; Borth, Nicole.

In: Biotechnology and Bioengineering, Vol. 113, No. 10, 10.2016, p. 2241-53.

Research output: Contribution to journalArticleResearchpeer-review

Feichtinger, J, Hernández, I, Fischer, C, Hanscho, M, Auer, N, Hackl, M, Jadhav, V, Baumann, M, Krempl, PM, Schmidl, C, Farlik, M, Schuster, M, Merkel, A, Sommer, A, Heath, S, Rico, D, Bock, C, Thallinger, GG & Borth, N 2016, 'Comprehensive genome and epigenome characterization of CHO cells in response to evolutionary pressures and over time' Biotechnology and Bioengineering, vol. 113, no. 10, pp. 2241-53. https://doi.org/10.1002/bit.25990
Feichtinger, Julia ; Hernández, Inmaculada ; Fischer, Christoph ; Hanscho, Michael ; Auer, Norbert ; Hackl, Matthias ; Jadhav, Vaibhav ; Baumann, Martina ; Krempl, Peter M ; Schmidl, Christian ; Farlik, Matthias ; Schuster, Michael ; Merkel, Angelika ; Sommer, Andreas ; Heath, Simon ; Rico, Daniel ; Bock, Christoph ; Thallinger, Gerhard G ; Borth, Nicole. / Comprehensive genome and epigenome characterization of CHO cells in response to evolutionary pressures and over time. In: Biotechnology and Bioengineering. 2016 ; Vol. 113, No. 10. pp. 2241-53.
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