%0 Journal Article %A Moerkens, Renée %A Mooiweer, Joram %A Smits, Eline %A Berg, Marijn %A Ramírez-Sánchez, Aarón D %A Modderman, Rutger %A Puschhof, Jens %A Pleguezuelos-Manzano, Cayetano %A Barrett, Robert J %A Wijmenga, Cisca %A Jonkers, Iris H %A Withoff, Sebo %T Gene expression profiling reveals enhanced nutrient and drug metabolism and maturation of hiPSC-derived intestine-on-chip relative to organoids and Transwells. %J Stem cell reports %V 20 %N 12 %@ 2213-6711 %C Maryland Heights, MO %I Cell Press %M DKFZ-2025-02440 %P 102715 %D 2025 %Z 2025 Dec 9;20(12):102715 %X The human intestinal epithelial barrier is shaped by biological and biomechanical cues, including growth factor gradients and fluid flow. While these factors are known to affect adult stem cell (ASC)-derived intestinal epithelial cells in vitro, their impact on human induced pluripotent stem cell (hiPSC)-derived cells is largely unexplored. Here, we compare the cellular composition and gene expression profiles of hiPSC-derived intestinal epithelial cells exposed to various medium compositions and cultured as organoids, in Transwell and microfluidic intestine-on-chip systems. Modulating key signaling pathways (WNT, NOTCH, bone morphogenetic protein [BMP], and mitogen-activated protein kinase [MAPK]) influenced the presence of dividing, absorptive, and secretory epithelial lineages. Upon differentiation, intestinal epithelial cells expressed genes encoding digestive enzymes, nutrient transporters, and drug-metabolizing enzymes. Notably, these pathways were most enhanced in the intestine-on-chip system, along with an expression profile that suggests a more mature state. These findings highlight the potential of hiPSC-derived intestinal cells to model important intestinal functions and guide the selection of optimal culture conditions for specific applications. %K Transwell (Other) %K differentiation medium (Other) %K gut-on-chip (Other) %K human (Other) %K induced pluripotent stem cell (Other) %K intestinal epithelial barrier (Other) %K intestine-on-chip (Other) %K organ-on-chip (Other) %K organoid (Other) %K small intestine (Other) %F PUB:(DE-HGF)16 %9 Journal Article %$ pmid:41237783 %R 10.1016/j.stemcr.2025.102715 %U https://inrepo02.dkfz.de/record/306211