Generation of human gastroid with fundic-antral patterningusing pluripotent stem cells v1

Current human gastric organoids are commonly generated using a stepwise process in which human pluripotent stem cells (hPSCs) are differentiated to epithelial-like posterior foregut (PFG) spheroids from definitive endoderm (DE) monolayer, before further development towards either fundic gastric organoids (FGO) or antral gastric organoids (AGO). However, the generation of human gastric organoids with asymmetric fundic-antral patterning remains challenging, which is possibly due to the lack of non-endodermal cell populations. Herein, we adopted a multi-lineage co-development strategy through either self-organization or engineered tissue assembly, which enabled the generation of a higher fidelity gastric development model, the gastroid, that could recapitulate the regional patterning along the fundic-antral axis in early stomach organogenesis.