GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE302nnn/GSE302458/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE302458GEOGSEfalseGeneration of expandable hepatocyte organoids with multipolar organization from human embryonic stem cellsIn this study, we successfully generated mature grape-like heporgs (G-heporg) from human embryonic stem cells (hESCs) using a modified hepatocyte organoid culture system. Within this differentiation platform, spherical hepatocyte organoids (S-heporg) spontaneously emerged alongside G-heporgs. Similar to primary heporgs, differentiated G-heporgs exhibited high ALB expression and expansion capability, whereas the S-heporgs lacked both characteristics. Comparative analysis revealed that IGF2 stimulates G-heporg formation. Moreover, we found that targeted modulation of the Hippo-YAP pathway overcame long-term expansion limitations in G-heporgs. Crucially, the differentiated and expandable G-heporgs developed multipolar architectures with functional BC networks, recapitulating the polarity characteristic of primary hepatocytes. Finally, we modeled copper ion metabolism using G-heporgs, demonstrating their utility for investigating polarized trafficking processes of hepatocyte metabolites2026/04/08GSE302458GSM9104380GSM9104391GSM9104381GSM9104392GSM9104390GSM9104388GSM9104399GSM9104389GSM9104397GSM9104386GSM9104387GSM9104398GSM9104384GSM9104395GSM9104385GSM9104396GSM9104393GSM9104382GSM9104383GSM9104394GSM910437924676302458Homo sapiens[41888105]