{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T14:04:37Z","timestamp":1788185077191,"version":"build-2803163510"},"reference-count":83,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["CRG\/2022\/007565"],"award-info":[{"award-number":["CRG\/2022\/007565"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotechnology Journal"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Chinese Hamster Ovary (CHO) cells are the predominant host for the production of biotherapeutics; however, there remains considerable potential to further enhance their cellular productivity. Adaptive laboratory evolution (ALE) combined with omics\u2010based analysis has emerged as a promising approach toward generating host cell lines with desirable characteristics. In this study, CHOK1 cells were gradually adapted to tunicamycin (TM), an endoplasmic reticulum (ER) stressor, resulting in an 8\u2010fold increase in resistance compared to the non\u2010adapted cells with a marked enlargement of the ER. Notably, the per\u2010cell secretion rate of total protein was 3\u2010 to 4\u2010fold higher in the TM\u2010adapted cells. Transcriptomic analysis revealed upregulation of several genes in the protein processing pathway, such as Dpagt1, the TM target gene, and ER stress response genes. The protein transport, secretion and ubiquitination pathways were also altered, potentially contributing to the increased protein secretion. Furthermore, genes participating in signaling cascades of PI3K\u2010AKT, MAPK, and Ras pathways were differentially expressed, thereby aiding in its survival and proliferation. Whole genome sequencing confirmed the amplification of a large genome segment of chromosome 4, which included several genes upregulated at the mRNA level, including Dpagt1. Thus, the survival and increased protein secretion of TM\u2010adapted cells can be attributed to a combination of transcriptional level changes and amplification of a large genome segment. Further, transient expression of a recombinant protein, SEAP, in TM\u2010adapted cells showed an improvement in specific productivity of \u223c1.4 fold as compared to the non\u2010adapted cells, underscoring the importance of ALE as a cell engineering strategy.<\/jats:p>","DOI":"10.1002\/biot.70163","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T13:31:23Z","timestamp":1765978283000},"source":"Crossref","is-referenced-by-count":1,"title":["Genome Amplification and Altered Transcriptome Aid in Survival and Enhanced Protein Secretion in Tunicamycin\u2010Resistant CHOK1 Cells"],"prefix":"10.1002","volume":"20","author":[{"given":"Priya","family":"Mishra","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering Indian Institute of Technology Bombay  Mumbai 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