PLX284001

GSE131921: Molecular characterization of a toxicological tipping point in human induced pluripotent stem cell (hiPSC)-derived endoderm exposed to all-trans retinoic acid (ATRA)

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Embryonic development commences with the formation of three germ layers from the primitive streak during gastrulation. The endoderm layer gives rise to the gut tube, leading to development of several internal organs, including the thyroid, thymus, lungs, stomach, liver, pancreas, and intestines. We differentiated human induced pluripotent stem cells (hiPSCs) to embryonic endoderm and sought to identify a tipping point at which the developing system did not recover from perturbations caused by exposure to a known teratogen, all-trans retinoic acid (ATRA). Differentiating iPSC-derived endoderm was exposed to five concentrations of ATRA between 0.001 and 10 M at 6h, 96h, or 192h and assessed for forkhead box A2 (FOXA2) protein expression and global gene transcript expression measured by RNA-sequencing. A tipping point of 1711 nM was identified where patterns of differentially expressed genes supported a shift in the developmental trajectory away from embryonic endoderm in favor of mesoderm and extraembryonic endoderm. SOURCE: Thomas Knudsen (knudsen.thomas@epa.gov) - US EPA