摘要：SummaryMulti-lineage development from gastruloids is enabling unprecedented opportunities to model and study human embryonic processes and is expected to accelerateex vivostrategies in organ development. Reproducing human cardiogenesis with neurogenesis in a multi-lineage context remains challenging, requiring spatiotemporal input of paracrine and mechanical cues. Here we extend elongating multi-lineage organized (EMLO) gastruloids to include cardiogenesis (EMLOC) and describe interconnected neuro-cardiac lineages in a single gastruloid model. Contractile EMLOCs recapitulate numerous interlinked developmental features including heart tube formation and specialization, cardiomyocyte differentiation and remodeling phases, epicardium, ventricular wall morphogenesis, chamber-like structures and formation of a putative outflow tract. The EMLOC cardiac region, which originates anterior to gut tube primordium, is progressively populated by neurons in a spatial pattern mirroring the known distribution of neurons in the innervated human heart. This human EMLOC model represents a multi-lineage advancement for the study of coincident neurogenesis and cardiogenesis.Graphical abstractDisplay OmittedHighlights•A trunk-biased microenvironment primed for cardiogenesis•Gastruloid-derived spatiotemporal features of cardiogenesis•Neurogenesis coupled with neuronal population of cardiac regions•Neuro-cardiac multi-lineage, multi-tissue linked developmental modelCell biology; Stem cell research; Genomics
