Spatial Proteomics Reveals Differences in the Cellular Architecture of Antibody-Producing CHO and Plasma Cell-Derived Cells.

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To meet the growing demand of these pharmaceuticals, CHO cells are under constant development in order to enhance their stability and productivity. The last decades saw a shift from empirical cell line optimization toward rational cell engineering using a growing number of large omics datasets to alter cell physiology on various levels. Especially proteomics workflows reached new levels in proteome coverage and data quality because of advances in high-resolution mass spectrometry instrumentation. One type of workflow concentrates on spatial proteomics by usage of subcellular fractionation of organelles with subsequent shotgun mass spectrometry proteomics and machine learning algorithms to determine the subcellular localization of large portions of the cellular proteome at a certain time point. Here, we present the first subcellular spatial proteome of a CHO-K1 cell line producing high titers of recombinant antibody in comparison to the spatial proteome of an antibody-producing plasma cell-derived myeloma cell line. Both cell lines show colocalization of immunoglobulin G chains with chaperones and proteins associated in protein glycosylation within the endoplasmic reticulum compartment. However, we report differences in the localization of proteins associated to vesicle-mediated transport, transcription, and translation, which may affect antibody production in both cell lines. Furthermore, pairing subcellular localization data with protein expression data revealed elevated protein masses for organelles in the secretory pathway in plasma cell-derived MPC-11 (Merwin plasma cell tumor-11) cells. Our study highlights the potential of subcellular spatial proteomics combined with protein expression as potent workflow to identify characteristics of highly efficient recombinant protein-expressing cell lines. Data are available via ProteomeXchange with identifier PXD029115.", "claims": [{"id": "claim-method", "statement": "Each distance was tested on statistical significance between CHO-K1 and MPC-11 maps (Student’s t test, BH-FDR = 0.05).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35934186", "locator": "sections[18] \"Detection of DL Proteins\" paragraph 2", "quote": "Each distance was tested on statistical significance between CHO-K1 and MPC-11 maps (Student’s t test, BH-FDR = 0.05)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The MS proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository (88) with the dataset identifier PXD029115 and 10.6019/PXD029115. MSMS spectra were deposited at MS-Viewer (89) with search keys mh4zluopbr (MPC-11 replicate 1), eubymniai5 (MPC-11 replicate 2), bxfcnm1haz (MPC-11 replicate 3), 6v9pkdfqig (CHO-K1 replicate 1), dlx2ixr12g (CHO-K1 replicate 2), zqhdi6zysy (CHO-K1 replicate 3), and e2fbeqkqp (unfractionated cell lysates of CHO-K1 and MPC-11 cells).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35934186", "locator": "sections[32] \"Data Availability\" paragraph 2", "quote": "The MS proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository (88) with the dataset identifier PXD029115 and 10.6019/PXD029115. MSMS spectra were deposited at MS-Viewer (89) with search keys mh4zluopbr (MPC-11 replicate 1), eubymniai5 (MPC-11 replicate 2), bxfcnm1haz (MPC-11 replicate 3), 6v9pkdfqig (CHO-K1 replicate 1), dlx2ixr12g (CHO-K1 replicate 2), zqhdi6zysy (CHO-K1 replicate 3), and e2fbeqkqp (unfractionated cell lysates of CHO-K1 and MPC-11 cells)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The paper reports spatial proteome maps for two antibody-secreting cell lines and identifies differences in protein localization, particularly for vesicle-mediated transport, transcription, and translation.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35934186", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Here, we present the first subcellular spatial proteome of a CHO-K1 cell line producing high titers of recombinant antibody in comparison to the spatial proteome of an antibody-producing plasma cell–derived myeloma cell line."}, {"asset": "source:pmid:35934186", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "However, we report differences in the localization of proteins associated to vesicle-mediated transport, transcription, and translation, which may affect antibody production in both cell lines."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The paper reports spatial proteome maps for two antibody-secreting cell lines and identifies differences in protein localization, particularly for vesicle-mediated transport, transcription, and translation.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:35934186"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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