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A proteomics approach to decipher a sticky CHO situation
Chinese hamster ovary (CHO) cells serve as protein therapeutics workhorses, so it is useful to understand what intrinsic properties make certain host cell lines and clones preferable for scale up and production of target proteins. In this study, two CHO host cell lines (H1, H2), and their respective...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9546176/ https://www.ncbi.nlm.nih.gov/pubmed/35470426 http://dx.doi.org/10.1002/bit.28108 |
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author | Kumar, Swetha Kumar, Amit Huhn, Steven DeVine, Lauren Cole, Robert Du, Zhimei Betenbaugh, Michael |
author_facet | Kumar, Swetha Kumar, Amit Huhn, Steven DeVine, Lauren Cole, Robert Du, Zhimei Betenbaugh, Michael |
author_sort | Kumar, Swetha |
collection | PubMed |
description | Chinese hamster ovary (CHO) cells serve as protein therapeutics workhorses, so it is useful to understand what intrinsic properties make certain host cell lines and clones preferable for scale up and production of target proteins. In this study, two CHO host cell lines (H1, H2), and their respective clones were evaluated using comparative TMT‐proteomics. The clones obtained from host H1 showed increased productivity (6.8 times higher) in comparison to clones from host H2. Based on fold‐change analyses, we observed differential regulation in pathways including cell adhesion, aggregation, and cellular metabolism among others. In particular, the cellular adhesion pathway was downregulated in H1, in which podoplanin, an antiadhesion molecule, was upregulated the most in host H1 and associated clones. Phenotypically, these cells were less likely to aggregate and adhere to surfaces. In addition, enzymes involved in cellular metabolism such as isocitrate dehydrogenase (IDH) and mitochondrial‐d‐lactate dehydrogenase ( d‐LDHm) were also found to be differentially regulated. IDH plays a key role in TCA cycle and isocitrate‐alpha‐ketoglutarate cycle while d‐LDHm aids in the elimination of toxic metabolite methylglyoxal, involved in protein degradation. These findings will enhance our efforts towards understanding why certain CHO cell lines exhibit enhanced performance and perhaps provide future cell engineering targets. |
format | Online Article Text |
id | pubmed-9546176 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95461762022-10-14 A proteomics approach to decipher a sticky CHO situation Kumar, Swetha Kumar, Amit Huhn, Steven DeVine, Lauren Cole, Robert Du, Zhimei Betenbaugh, Michael Biotechnol Bioeng ARTICLES Chinese hamster ovary (CHO) cells serve as protein therapeutics workhorses, so it is useful to understand what intrinsic properties make certain host cell lines and clones preferable for scale up and production of target proteins. In this study, two CHO host cell lines (H1, H2), and their respective clones were evaluated using comparative TMT‐proteomics. The clones obtained from host H1 showed increased productivity (6.8 times higher) in comparison to clones from host H2. Based on fold‐change analyses, we observed differential regulation in pathways including cell adhesion, aggregation, and cellular metabolism among others. In particular, the cellular adhesion pathway was downregulated in H1, in which podoplanin, an antiadhesion molecule, was upregulated the most in host H1 and associated clones. Phenotypically, these cells were less likely to aggregate and adhere to surfaces. In addition, enzymes involved in cellular metabolism such as isocitrate dehydrogenase (IDH) and mitochondrial‐d‐lactate dehydrogenase ( d‐LDHm) were also found to be differentially regulated. IDH plays a key role in TCA cycle and isocitrate‐alpha‐ketoglutarate cycle while d‐LDHm aids in the elimination of toxic metabolite methylglyoxal, involved in protein degradation. These findings will enhance our efforts towards understanding why certain CHO cell lines exhibit enhanced performance and perhaps provide future cell engineering targets. John Wiley and Sons Inc. 2022-05-25 2022-08 /pmc/articles/PMC9546176/ /pubmed/35470426 http://dx.doi.org/10.1002/bit.28108 Text en © 2022 Merck Sharp & Dohme LLC. Biotechnology and Bioengineering published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | ARTICLES Kumar, Swetha Kumar, Amit Huhn, Steven DeVine, Lauren Cole, Robert Du, Zhimei Betenbaugh, Michael A proteomics approach to decipher a sticky CHO situation |
title | A proteomics approach to decipher a sticky CHO situation |
title_full | A proteomics approach to decipher a sticky CHO situation |
title_fullStr | A proteomics approach to decipher a sticky CHO situation |
title_full_unstemmed | A proteomics approach to decipher a sticky CHO situation |
title_short | A proteomics approach to decipher a sticky CHO situation |
title_sort | proteomics approach to decipher a sticky cho situation |
topic | ARTICLES |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9546176/ https://www.ncbi.nlm.nih.gov/pubmed/35470426 http://dx.doi.org/10.1002/bit.28108 |
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