{"doi":"10.1021/acs.jproteome.1c00611","title":"Multiomics Method Enabled by Sequential Metabolomics and Proteomics for Human Pluripotent Stem-Cell-Derived Cardiomyocytes","abstract":"Human pluripotent stem-cell-derived cardiomyocytes (hPSC-CMs) show immense promise for patient-specific disease modeling, cardiotoxicity screening, and regenerative therapy development. However, thus far, hPSC-CMs in culture have not recapitulated the structural or functional properties of adult CMs in vivo. To gain global insight into hPSC-CM biology, we established a multiomics method for analyzing the hPSC-CM metabolome and proteome from the same cell culture, creating multidimensional profiles of hPSC-CMs. Specifically, we developed a sequential extraction to capture metabolites and proteins from the same hPSC-CM monolayer cultures and analyzed these extracts using high-resolution mass spectrometry. Using this method, we annotated 205 metabolites/lipids and 4319 proteins from 106 cells with high reproducibility. We further integrated the proteome and metabolome measurements to create network profiles of molecular phenotypes for hPSC-CMs. Out of 310 pathways identified using metabolomics and proteomics, 40 pathways were considered significantly overrepresented (false-discovery-rate-corrected p ≤ 0.05). Highly populated pathways included those involved in protein synthesis (ribosome, spliceosome), ATP generation (oxidative phosphorylation), and cardiac muscle contraction. This multiomics method achieves a deep coverage of metabolites and proteins, creating a multidimensional view of the hPSC-CM phenotype, which provides a strong technological foundation to advance the understanding of hPSC-CM biology. Raw data are available in the MassIVE repository with identifier MSV000088010.","journal":"Journal of Proteome Research","year":2021,"id":161055,"datarank":0.9375121777477867,"base_score":3.4339872044851463,"endowment":3.4339872044851463,"self_citation_contribution":0.515098080672772,"citation_network_contribution":0.42241409707501476,"self_endowment_contribution":0.515098080672772,"citer_contribution":0.42241409707501476,"corpus_percentile":null,"corpus_rank":null,"citation_count":30,"citer_count":18,"citers_with_citation_signal":15,"citers_with_endowment":15,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":414476,"name":"Aaron D. Simmons","orcid":"0000-0001-6608-0320","position":1,"is_corresponding":false},{"id":298234,"name":"David S. Roberts","orcid":"0000-0002-0478-4987","position":2,"is_corresponding":false},{"id":301519,"name":"Yanlong Zhu","orcid":"0000-0003-4909-7336","position":3,"is_corresponding":false},{"id":347400,"name":"Timothy J. Aballo","orcid":"0000-0003-1164-5966","position":4,"is_corresponding":false},{"id":331808,"name":"Benjamin Wancewicz","orcid":"0000-0002-6833-1709","position":5,"is_corresponding":false},{"id":254957,"name":"Sean P. Palecek","orcid":"0000-0003-4917-5584","position":6,"is_corresponding":false},{"id":256465,"name":"Ying Ge","orcid":"0000-0001-5211-6812","position":7,"is_corresponding":false},{"id":275524,"name":"Elizabeth F. Bayne","orcid":"0000-0002-6252-2934","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:44:52.299342Z","pmid":"34499502","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}