TY  - JOUR
AU  - Moerkens, Renée
AU  - Mooiweer, Joram
AU  - Smits, Eline
AU  - Berg, Marijn
AU  - Ramírez-Sánchez, Aarón D
AU  - Modderman, Rutger
AU  - Puschhof, Jens
AU  - Pleguezuelos-Manzano, Cayetano
AU  - Barrett, Robert J
AU  - Wijmenga, Cisca
AU  - Jonkers, Iris H
AU  - Withoff, Sebo
TI  - Gene expression profiling reveals enhanced nutrient and drug metabolism and maturation of hiPSC-derived intestine-on-chip relative to organoids and Transwells.
JO  - Stem cell reports
VL  - 20
IS  - 12
SN  - 2213-6711
CY  - Maryland Heights, MO
PB  - Cell Press
M1  - DKFZ-2025-02440
SP  - 102715
PY  - 2025
N1  - 2025 Dec 9;20(12):102715
AB  - 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.
KW  - Transwell (Other)
KW  - differentiation medium (Other)
KW  - gut-on-chip (Other)
KW  - human (Other)
KW  - induced pluripotent stem cell (Other)
KW  - intestinal epithelial barrier (Other)
KW  - intestine-on-chip (Other)
KW  - organ-on-chip (Other)
KW  - organoid (Other)
KW  - small intestine (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:41237783
DO  - DOI:10.1016/j.stemcr.2025.102715
UR  - https://inrepo02.dkfz.de/record/306211
ER  -