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Karyotype variation of CHO host cell lines over time in culture characterized by chromosome counting and chromosome painting
Author(s) -
Vcelar Sabine,
Jadhav Vaibhav,
Melcher Michael,
Auer Norbert,
Hrdina Astrid,
Sagmeister Rebecca,
Heffner Kelley,
Puklowski Anja,
Betenbaugh Michael,
Wenger Till,
Leisch Friedrich,
Baumann Martina,
Borth Nicole
Publication year - 2018
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.26453
Subject(s) - chinese hamster ovary cell , karyotype , biology , population , chromosome , genetics , chinese hamster , cell culture , microbiology and biotechnology , gene , demography , sociology
Genomic rearrangements are a common phenomenon in rapidly growing cell lines such as Chinese hamster ovary (CHO) cells, a feature that in the context of production of biologics may lead to cell line and product instability. Few methods exist to assess such genome wide instability. Here, we use the population distribution of chromosome numbers per cell as well as chromosome painting to quantify the karyotypic variation in several CHO host cell lines. CHO‐S, CHO‐K1 8 mM glutamine, and CHO‐K1 cells adapted to grow in media containing no glutamine were analyzed over up to 6 months in culture. All three cell lines were clearly distinguishable by their chromosome number distribution and by the specific chromosome rearrangements that were present in each population. Chromosome Painting revealed a predominant karyotype for each cell line at the start of the experiment, completed by a large number of variants present in each population. Over time in culture, the predominant karyotype changed for CHO‐S and CHO‐K1, with the diversity increasing and new variants appearing, while CHO‐K1 0 mM Gln preferred chromosome pattern increased in percent of the population over time. As control, Chinese hamster lung fibroblasts were shown to also contain an increasing number of variants over time in culture.