title: Genetic analysis of the clonal stability of Chinese hamster ovary cells for recombinant protein production.
abstract: Chinese hamster ovary (CHO) cells are frequently used for the production of recombinant proteins for therapeutical applications. However, the recombinant protein expression level of CHO cells may reduce during long-term culture. The physiological changes related to the stability of expression were not well understood. In this study, we performed a series of genetic analysis on stable and unstable clonal derived populations. Transcriptome analysis revealed that a large number of differentially expressed genes (>100) were identified in the unstable population between early and late generations, while only a few differentially expressed genes were found in the stable population, suggesting that the gene expression change is related to the instability of recombinant protein production. On the other hand, no significant differences were found in promoter methylation or gene copy numbers in the unstable population. Taken together, our data help better understand the molecular mechanism underlying the stability of recombinant protein production in CHO cells.
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai, China. jfang@tongji.edu.cn.
authors.forename: Hongwen
authors.initials: H
authors.lastname: Li
authors.forename: Kaiming
authors.initials: K
authors.lastname: Chen
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Jiannan
authors.initials: J
authors.lastname: Lin
authors.forename: Chao
authors.initials: C
authors.lastname: Yu
authors.forename: Fang
authors.initials: F
authors.lastname: Yu
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.forename: Cizhong
authors.initials: C
authors.lastname: Jiang
authors.forename: Hua
authors.initials: H
authors.lastname: Gu
authors.forename: Jianmin
authors.initials: J
authors.lastname: Fang
mesh_terms: D000818:Animals; D016466:CHO Cells / Q000378:metabolism*; D060965:Clonal Evolution / Q000235:genetics*; D002999:Clone Cells; D019295:Computational Biology / Q000379:methods; D003412:Cricetulus; D019175:DNA Methylation; D018628:Gene Dosage; D020869:Gene Expression Profiling; D063990:Gene Ontology; D042822:Genomic Instability; D059014:High-Throughput Nucleotide Sequencing; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000096:biosynthesis*; D059467:Transcriptome
chemical_list: D011994:Recombinant Proteins