{"doi":"10.1016/j.celrep.2020.108117","title":"iPSC Modeling of RBM20-Deficient DCM Identifies Upregulation of RBM20 as a Therapeutic Strategy","abstract":"Recent advances in induced pluripotent stem cell (iPSC) technology and directed differentiation of iPSCs into cardiomyocytes (iPSC-CMs) make it possible to model genetic heart disease in vitro. We apply CRISPR/Cas9 genome editing technology to introduce three RBM20 mutations in iPSCs and differentiate them into iPSC-CMs to establish an in vitro model of RBM20 mutant dilated cardiomyopathy (DCM). In iPSC-CMs harboring a known causal RBM20 variant, the splicing of RBM20 target genes, calcium handling, and contractility are impaired consistent with the disease manifestation in patients. A variant (Pro633Leu) identified by exome sequencing of patient genomes displays the same disease phenotypes, thus establishing this variant as disease causing. We find that all-trans retinoic acid upregulates RBM20 expression and reverts the splicing, calcium handling, and contractility defects in iPSC-CMs with different causal RBM20 mutations. These results suggest that pharmacological upregulation of RBM20 expression is a promising therapeutic strategy for DCM patients with a heterozygous mutation in RBM20.","journal":"Cell Reports","year":2020,"id":58365,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":73,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9514,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":90170,"name":"Han Sun","orcid":"0000-0002-3390-0027","position":1,"is_corresponding":false},{"id":282724,"name":"Wei Wu","orcid":"0000-0001-5643-8739","position":2,"is_corresponding":false},{"id":306679,"name":"Jingyan Wu","orcid":null,"position":3,"is_corresponding":false},{"id":49797,"name":"Chenchen Zhu","orcid":"0000-0003-2165-9456","position":4,"is_corresponding":false},{"id":305676,"name":"Martin Liss","orcid":"0000-0002-0585-7850","position":5,"is_corresponding":false},{"id":305677,"name":"Ioannis Karakikes","orcid":"0000-0002-4348-600X","position":6,"is_corresponding":false},{"id":17268,"name":"Shannon Rego","orcid":"0000-0003-1910-7441","position":7,"is_corresponding":false},{"id":305678,"name":"Andrea Cipriano","orcid":"0000-0003-0775-3198","position":8,"is_corresponding":false},{"id":5648,"name":"Michael P. Snyder","orcid":"0000-0003-0784-7987","position":9,"is_corresponding":false},{"id":305679,"name":"Benjamin Meder","orcid":"0000-0003-0741-2633","position":10,"is_corresponding":false},{"id":305680,"name":"Zhenyu Xu","orcid":"0000-0002-3484-9147","position":11,"is_corresponding":false},{"id":305681,"name":"Gilles Millat","orcid":"0000-0001-6127-0694","position":12,"is_corresponding":false},{"id":305682,"name":"Michael Gotthardt","orcid":"0000-0003-1788-3172","position":13,"is_corresponding":false},{"id":229040,"name":"Mark Mercola","orcid":"0000-0002-1430-2013","position":14,"is_corresponding":false},{"id":4994,"name":"Lars M. Steinmetz","orcid":"0000-0002-3962-2865","position":15,"is_corresponding":false},{"id":229024,"name":"Francesca Briganti","orcid":"0000-0001-5738-2642","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-18T21:07:11.345501Z","pmid":"32905764","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":[]}