biostudies-literatureUnknownHoang PNICHD NIH HHSNIDDK NIH HHSNHLBI NIH HHSThe 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 highligbioRxiv : the preprint server for biology2025.09.17.676874https://www.ebi.ac.uk/biostudies/studies/S-EPMC12458260biostudies-literatureSize-Modulated Mesoderm-Endoderm Divergence and Myocardial Cavitation in Micropatterned Cardioids.PMC12458260R56 DK133147R15 HD108720R01 HL175050R01 HD101130Yang HChai MZheng YLian XLMa ZDe Vlaminck ICosgrove BDHoang PMcKellar DWMai NYTucker NAmack JKowalczewski AfalseSize-Modulated Mesoderm-Endoderm Divergence and Myocardial Cavitation in Micropatterned Cardioids.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 highlig2025-01-01T00:00:00Z2025 Sep2026-05-03T03:11:06.669Z2026-05-03T03:10:09.167ZS-EPMC124582604100091710.1101/2025.09.17.676874