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比较系统组学阐明 CHO 和 SP2/0 细胞系之间的生理差异。

Comparative systeomics to elucidate physiological differences between CHO and SP2/0 cell lines.

机构信息

Department of Natural Sciences, Acibadem Mehmet Ali Aydınlar University, Istanbul, Turkey.

Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.

出版信息

Sci Rep. 2022 Feb 28;12(1):3280. doi: 10.1038/s41598-022-06886-1.

DOI:10.1038/s41598-022-06886-1
PMID:35228567
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8885639/
Abstract

Omics-based tools were coupled with bioinformatics for a systeomics analysis of two biopharma cell types: Chinese hamster ovary (M-CHO and CHO-K1) and SP2/0. Exponential and stationary phase samples revealed more than 10,000 transcripts and 6000 proteins across these two manufacturing cell lines. A statistical comparison of transcriptomics and proteomics data identified downregulated genes involved in protein folding, protein synthesis and protein metabolism, including PPIA-cyclophilin A, HSPD1, and EIF3K, in M-CHO compared to SP2/0 while cell cycle and actin cytoskeleton genes were reduced in SP2/0. KEGG pathway comparisons revealed glycerolipids, glycosphingolipids, ABC transporters, calcium signaling, cell adhesion, and secretion pathways depleted in M-CHO while retinol metabolism was upregulated. KEGG and IPA also indicated apoptosis, RNA degradation, and proteosomes enriched in CHO stationary phase. Alternatively, gene ontology analysis revealed an underrepresentation in ion and potassium channel activities, membrane proteins, and secretory granules including Stxbpt2, Syt1, Syt9, and Cma1 proteins in M-CHO. Additional enrichment strategies involving ultracentrifugation, biotinylation, and hydrazide chemistry identified over 4000 potential CHO membrane and secretory proteins, yet many secretory and membrane proteins were still depleted. This systeomics pipeline has revealed bottlenecks and potential opportunities for cell line engineering in CHO and SP2/0 to improve their production capabilities.

摘要

基于组学的工具与生物信息学相结合，对两种生物制药细胞系（中国仓鼠卵巢（M-CHO 和 CHO-K1）和 SP2/0）进行了系统组学分析。在这两个生产细胞系中，指数期和静止期样品揭示了超过 10000 个转录本和 6000 个蛋白质。转录组学和蛋白质组学数据的统计比较鉴定了下调的基因，这些基因涉及蛋白质折叠、蛋白质合成和蛋白质代谢，包括 M-CHO 中与 SP2/0 相比下调的 PPIA-细胞色素 P450 A、HSPD1 和 EIF3K，而 SP2/0 中细胞周期和肌动蛋白细胞骨架基因减少。KEGG 途径比较显示 M-CHO 中甘油磷脂、糖脂、ABC 转运蛋白、钙信号、细胞黏附和分泌途径减少，而视黄醇代谢上调。KEGG 和 IPA 还表明，CHO 静止期细胞凋亡、RNA 降解和蛋白酶体富集。相反，基因本体论分析显示 M-CHO 中离子和钾通道活性、膜蛋白和分泌颗粒减少，包括 Stxbpt2、Syt1、Syt9 和 Cma1 蛋白。涉及超速离心、生物素化和酰肼化学的其他富集策略鉴定了超过 4000 种潜在的 CHO 膜和分泌蛋白，但许多分泌和膜蛋白仍然减少。这个系统组学管道揭示了 CHO 和 SP2/0 细胞系工程的瓶颈和潜在机会，以提高它们的生产能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9bf/8885639/3e64d0ac7c03/41598_2022_6886_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9bf/8885639/6590c1c4cf06/41598_2022_6886_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9bf/8885639/f36db8aa9542/41598_2022_6886_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9bf/8885639/77f4dd24a0d6/41598_2022_6886_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9bf/8885639/b9469840351b/41598_2022_6886_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9bf/8885639/3e64d0ac7c03/41598_2022_6886_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9bf/8885639/6590c1c4cf06/41598_2022_6886_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9bf/8885639/fabec87217da/41598_2022_6886_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9bf/8885639/f36db8aa9542/41598_2022_6886_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9bf/8885639/77f4dd24a0d6/41598_2022_6886_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9bf/8885639/b9469840351b/41598_2022_6886_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9bf/8885639/3e64d0ac7c03/41598_2022_6886_Fig6_HTML.jpg

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