FIGURE 1. Generation of Human Intestinal Organoids with an Enteric Nervous System.
Schematic for generating human intestinal organoids (HIO) and vagal neural crest cells (NCC) through directed differentiation of human pluripotent stem cells. Activin A mediates efficient differentiation into definitive endoderm and WNT activation, using CHIR99021, in combination with FGF4 induces midgut endoderm monolayers and free-floating spheroids. FGF and EGF mediate differentiation into NCCs. Retinoic acid posteriorizes the NCCs into vagal NCCs. HIOs and NCCs are generated separately, combined by low-speed centrifugation, embedded in Matrigel and grown for 4 weeks in vitro.