Highlights d A hPSC-derived cell and organoid platform is used to study SARS-CoV-2 tissue tropism d Human pancreatic alpha and beta cells are permissive to SARS-CoV-2 infection d Human hepatocyte and cholangiocyte organoids are permissive to SARS-CoV-2 infection d hPSC-derived cells/organoids show similar chemokine responses as COVID-19 tissues

SUMMARYRecent lineage-tracing studies have produced conflicting results about whether the epicardium is a source of cardiac muscle cells during heart development. Here, we examined the developmental potential of epicardial tissue in zebrafish during both embryonic development and injury-induced heart regeneration. We found that upstream sequences of the transcription factor gene tcf21 activated robust, epicardium-specific expression throughout development and regeneration. Cre recombinase-based, genetic fate-mapping of larval or adult tcf21 + cells revealed contributions to perivascular cells, but not cardiomyocytes, during each form of cardiogenesis. Our findings indicate that natural epicardial fates are limited to non-myocardial cell types in zebrafish.

As vertebrate embryos develop to adulthood, their organs dramatically increase size and change tissue architecture. Here, we used a multicolor clonal analysis to define contributions of many individual cardiomyocytes as the zebrafish heart undergoes morphogenesis from a primitive embryonic structure into its complex adult form. We find that the single cardiomyocyte-thick wall of the juvenile ventricle forms by lateral expansion of several dozen cardiomyocytes into muscle patches of variable sizes and shapes. As juveniles mature into adults, this structure becomes fully enveloped by a new lineage of cortical muscle. Adult cortical muscle originates from a small number (~8) of cardiomyocytes that display clonal dominance reminiscent of stem cell populations. Cortical cardiomyocytes initially emerge from internal myofibers that in rare events breach the juvenile ventricular wall and expand over the surface. Our study illuminates dynamic proliferative behaviors that generate adult cardiac structure, revealing clonal dominance as a key mechanism that shapes a vertebrate organ.