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dc.contributor.author
Tossolini, Ileana del Rosario
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López Díaz, Fernando Javier
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Kratje, Ricardo Bertoldo
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Prieto, Claudio
dc.date.available
2019-10-01T17:53:10Z
dc.date.issued
2018-11
dc.identifier.citation
Tossolini, Ileana del Rosario; López Díaz, Fernando Javier; Kratje, Ricardo Bertoldo; Prieto, Claudio; Characterization of cellular states of CHO-K1 suspension cell culture through cell cycle and RNA-sequencing profiling; Elsevier Science; Journal of Biotechnology; 286; 11-2018; 56-67
dc.identifier.issn
0168-1656
dc.identifier.uri
http://hdl.handle.net/11336/84939
dc.description.abstract
Chinese hamster ovary (CHO) derived cell lines are the preferred host system for the production of therapeutic proteins. The aim of this work was to explore the regulation of suspension-adapted CHO-K1 host cell line bioprocesses, especially under a temperature gradient from 37 °C to 31 °C. We analyzed cell cycle behavior through flow cytometry of propidium iodide stained cells and high throughput transcriptome dynamics by RNA sequencing. We found a cell culture state characterized by G0/G1 synchronization, mainly during the late exponential growth phase and towards the last days of the stationary phase. We successfully identified key genes and pathways connected with the particular culture states, such as response to low temperature, modulation of the cell cycle, regulation of DNA replication and repair, apoptosis, among others. The most important gene expression changes occurred throughout the stationary phase when gene up-regulation markedly prevailed. Our RNA-seq data analysis enabled the identification of target genes for mechanism-based cell line engineering and bioprocess modification, an essential step to translate gene expression data from CHO-K1 host cells into bioprocess-related knowledge. Further efforts aim at increasing desirable phenotypes of CHO cells, and promoting efficient production of high quality therapeutic proteins can highly benefit from this type of studies.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier Science
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
CELL CYCLE
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CHO-K1 CELLS
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RNA-SEQ
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TRANSCRIPTOME ANALYSIS
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Otras Biotecnologías de la Salud
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Biotecnología de la Salud
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Characterization of cellular states of CHO-K1 suspension cell culture through cell cycle and RNA-sequencing profiling
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-09-27T14:56:23Z
dc.journal.volume
286
dc.journal.pagination
56-67
dc.journal.pais
Países Bajos
dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Tossolini, Ileana del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina
dc.description.fil
Fil: López Díaz, Fernando Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Intellectics Inc.; Estados Unidos. Salk Institute for Biological Studies; Estados Unidos
dc.description.fil
Fil: Kratje, Ricardo Bertoldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina
dc.description.fil
Fil: Prieto, Claudio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina. Cellargen Biotech S.R.L.; Argentina
dc.journal.title
Journal of Biotechnology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0168165618306424
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1016/j.jbiotec.2018.09.007
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