Loss of TBX3 enhances pancreatic progenitor generation from human pluripotent stem cells [Hepatoblast RNA-seq]

Tbx3 regulates liver development in the mouse, but it's role in human liver development is unclear. We generated TBX3 knockout pluripotent stem cell lines and found that liver differentiation is also impaired in humans. Interestingly we noted expression of pancreas-specific genes during the liver differentiation in the TBX3 knockout line. To further investigate this phenomenon, we performed RNA-seq on cells at the hepatoblast stage of the liver differentiation. These studies demonstrated that the loss of TBX3 enhances pancreatic-gene signature, implicating TBX3 as a regulator of fate decisions. Overall design: Wildtype and TBX3 knockout plurpotent stem cells lines were differentiated to hepatocytes. mRNA gene expression profiles were examined at the heptoblast stage of the liver differentiation (Day 12 Hepatoblast stage). Three biological replicates were analyzed for each stage (two genotypes, one stage per genotype)