{"doi":"10.1016/j.celrep.2023.112330","title":"Trajectory reconstruction identifies dysregulation of perinatal maturation programs in pluripotent stem cell-derived cardiomyocytes","abstract":"A limitation in the application of pluripotent stem cell-derived cardiomyocytes (PSC-CMs) is the failure of these cells to achieve full functional maturity. The mechanisms by which directed differentiation differs from endogenous development, leading to consequent PSC-CM maturation arrest, remain unclear. Here, we generate a single-cell RNA sequencing (scRNA-seq) reference of mouse in vivo CM maturation with extensive sampling of previously difficult-to-isolate perinatal time periods. We subsequently generate isogenic embryonic stem cells to create an in vitro scRNA-seq reference of PSC-CM-directed differentiation. Through trajectory reconstruction, we identify an endogenous perinatal maturation program that is poorly recapitulated in vitro. By comparison with published human datasets, we identify a network of nine transcription factors (TFs) whose targets are consistently dysregulated in PSC-CMs across species. Notably, these TFs are only partially activated in common ex vivo approaches to engineer PSC-CM maturation. Our study can be leveraged toward improving the clinical viability of PSC-CMs.","journal":"Cell Reports","year":2023,"id":335227,"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":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.6958,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":557744,"name":"Matthew Miyamoto","orcid":"0000-0002-2140-6769","position":1,"is_corresponding":false},{"id":561426,"name":"Renjun Zhu","orcid":null,"position":2,"is_corresponding":false},{"id":828265,"name":"Michaela Lynott","orcid":null,"position":3,"is_corresponding":false},{"id":684770,"name":"Jason Guo","orcid":"0000-0003-0062-5118","position":4,"is_corresponding":false},{"id":1064615,"name":"Elaine Zhelan Chen","orcid":"0000-0003-4061-7921","position":5,"is_corresponding":false},{"id":331356,"name":"Alexandre R. Colas","orcid":"0000-0001-8489-0570","position":6,"is_corresponding":false},{"id":557743,"name":"Brian L. Lin","orcid":"0000-0003-0800-7103","position":7,"is_corresponding":false},{"id":560952,"name":"Chulan Kwon","orcid":"0000-0002-4924-2778","position":8,"is_corresponding":false},{"id":557742,"name":"Suraj Kannan","orcid":"0000-0002-7820-7381","position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":null,"created_at":"2026-07-19T01:09:58.338267Z","pmid":"37014753","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":[]}