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Mammalian Systems Biotechnology Reveals Global Cellular Adaptations in a Recombinant CHO Cell Line.
Yusufi, Faraaz Noor Khan; Lakshmanan, Meiyappan; Ho, Ying Swan; Loo, Bernard Liat Wen; Ariyaratne, Pramila; Yang, Yuansheng; Ng, Say Kong; Tan, Tessa Rui Min; Yeo, Hock Chuan; Lim, Hsueh Lee; Ng, Sze Wai; Hiu, Ai Ping; Chow, Chung Ping; Wan, Corrine; Chen, Shuwen; Teo, Gavin; Song, Gao; Chin, Ju Xin; Ruan, Xiaoan; Sung, Ken Wing Kin; Hu, Wei-Shou; Yap, Miranda Gek Sim; Bardor, Muriel; Nagarajan, Niranjan; Lee, Dong-Yup.
Afiliación
  • Yusufi FNK; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
  • Lakshmanan M; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
  • Ho YS; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
  • Loo BLW; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
  • Ariyaratne P; Genome Institute of Singapore, Agency for Science, Technology and Research (A(∗)STAR), 60 Biopolis Street, #02-01 Genome, Singapore 138672, Singapore.
  • Yang Y; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
  • Ng SK; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
  • Tan TRM; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
  • Yeo HC; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore; Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117576, Singapore.
  • Lim HL; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
  • Ng SW; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
  • Hiu AP; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
  • Chow CP; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
  • Wan C; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
  • Chen S; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
  • Teo G; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
  • Song G; Genome Institute of Singapore, Agency for Science, Technology and Research (A(∗)STAR), 60 Biopolis Street, #02-01 Genome, Singapore 138672, Singapore.
  • Chin JX; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
  • Ruan X; Genome Institute of Singapore, Agency for Science, Technology and Research (A(∗)STAR), 60 Biopolis Street, #02-01 Genome, Singapore 138672, Singapore.
  • Sung KWK; Genome Institute of Singapore, Agency for Science, Technology and Research (A(∗)STAR), 60 Biopolis Street, #02-01 Genome, Singapore 138672, Singapore.
  • Hu WS; Department of Chemical Engineering and Materials Science, University of Minnesota, 421 Washington Avenue Southeast, Minneapolis, MN 55455-0132, USA.
  • Yap MGS; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore; Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117576, Singapore.
  • Bardor M; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore; Laboratoire Glycobiologie et Matrice Extracellulaire Végétale (Glyco-MEV), UNIROUEN, Normandie Université, 76000 Rouen, France.
  • Nagarajan N; Genome Institute of Singapore, Agency for Science, Technology and Research (A(∗)STAR), 60 Biopolis Street, #02-01 Genome, Singapore 138672, Singapore. Electronic address: nagarajann@gis.a-star.edu.sg.
  • Lee DY; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore; Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117576, Singapore. E
Cell Syst ; 4(5): 530-542.e6, 2017 05 24.
Article en En | MEDLINE | ID: mdl-28544881
Effective development of host cells for therapeutic protein production is hampered by the poor characterization of cellular transfection. Here, we employed a multi-omics-based systems biotechnology approach to elucidate the genotypic and phenotypic differences between a wild-type and recombinant antibody-producing Chinese hamster ovary (CHO) cell line. At the genomic level, we observed extensive rearrangements in specific targeted loci linked to transgene integration sites. Transcriptional re-wiring of DNA damage repair and cellular metabolism in the antibody producer, via changes in gene copy numbers, was also detected. Subsequent integration of transcriptomic data with a genome-scale metabolic model showed a substantial increase in energy metabolism in the antibody producer. Metabolomics, lipidomics, and glycomics analyses revealed an elevation in long-chain lipid species, potentially associated with protein transport and secretion requirements, and a surprising stability of N-glycosylation profiles between both cell lines. Overall, the proposed knowledge-based systems biotechnology framework can further accelerate mammalian cell-line engineering in a targeted manner.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Recombinantes / Células CHO / Biología de Sistemas Límite: Animals Idioma: En Revista: Cell Syst Año: 2017 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Recombinantes / Células CHO / Biología de Sistemas Límite: Animals Idioma: En Revista: Cell Syst Año: 2017 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Estados Unidos