{"doi":"10.1101/2025.09.17.676874","title":"Size-Modulated Mesoderm-Endoderm Divergence and Myocardial Cavitation in Micropatterned Cardioids","abstract":"The human heart, originating from the splanchnic mesoderm, is the first functional organ to develop, co-evolving with the foregut endoderm through reciprocal signaling. Previously, cardioid models offered new insights on cardiovascular cell lineages and tissue morphogenesis during heart development, while mesoderm-endoderm crosstalk remain incompletely understood. Here, we integrated micropatterned cardioids, CRISPR-engineered reporter hiPSCs, deep-tissue imaging, and single-cell RNA sequencing (scRNA-seq) to explore synergistic mesoderm-endoderm co-development. scRNA-seq with PHATE trajectory mapping reconstructed lineage bifurcations of mesoderm-heart and endoderm-foregut lineages, identifying key cell types in cardiac and hepatic development. Ligand-receptor interaction analysis highlighted mesodermal cells enriched in non-canonical WNT, NRG, and TGF-β signaling, while endodermal cells exhibited VEGF and Hedgehog activity. We found that micropattern sizes influenced cellular composition, cardioid cavitation, contractile functions, and mesoderm-endoderm signaling crosstalk. The cardioids generated from 600 μm diameter circle patterns showed larger cavity formation resembling early heart chamber formation. Our findings establish micropatterned cardioids as a model for mesoderm-endoderm co-development, enhancing our understanding of heart-foregut synergy during early embryogenesis.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":575314,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9338,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":622736,"name":"David W. McKellar","orcid":"0000-0002-7752-078X","position":1,"is_corresponding":false},{"id":734089,"name":"Andrew Kowalczewski","orcid":"0000-0002-9629-700X","position":2,"is_corresponding":false},{"id":1229401,"name":"Nhu Y","orcid":"0000-0001-6395-2875","position":3,"is_corresponding":false},{"id":1483620,"name":"Meng Chai","orcid":null,"position":4,"is_corresponding":false},{"id":270356,"name":"Xiaojun Lian","orcid":"0000-0002-9161-1004","position":5,"is_corresponding":false},{"id":1483247,"name":"Yi Zheng","orcid":"0000-0002-7979-1292","position":6,"is_corresponding":false},{"id":355298,"name":"Jeffrey D. Amack","orcid":"0000-0002-5465-9754","position":7,"is_corresponding":false},{"id":1483621,"name":"Nathan Tucker","orcid":null,"position":8,"is_corresponding":false},{"id":94489,"name":"Iwijn De Vlaminck","orcid":"0000-0001-6085-7311","position":9,"is_corresponding":false},{"id":317681,"name":"Huaxiao Yang","orcid":"0000-0001-9335-8201","position":10,"is_corresponding":false},{"id":230535,"name":"Benjamin D. Cosgrove","orcid":"0000-0003-2164-350X","position":11,"is_corresponding":false},{"id":571621,"name":"Zhen Ma","orcid":"0000-0001-5228-105X","position":12,"is_corresponding":false},{"id":966867,"name":"Plansky Hoang","orcid":"0000-0002-1255-9587","position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:57:48.486077Z","pmid":"41000917","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":[]}