The GLI-code controls HNF1A levels during in-vitro foregut differentiation

Differentiation of human induced pluripotent stem cells towards pancreatic islet endocrine cells is a complex process, involving the stepwise modulation of key developmental pathways, such as the Hedgehog signaling inhibition during early differentiation stages. In tandem with this active inhibition, key transcription factors for the islet endocrine cell fate, such as HNF1A, show specific changes in their expression patterns. Here we designed a forthright pilot study aimed at investigating the potential interconnection between HH-signaling inhibition and the increase in the HNF1A expression during early regeneration, by inducing changes in the GLI code. This unveiled a link between the two, where GLI3-R mediated Hedgehog target genes inhibition is apparently required for HNF1A efficient expression. PGP1 iPSc were differentiated toward pancreatic endocine cell fate following the differentiation protocol by Rezania 2014. At different stage 3, 4, 5, 6, and 7 samples were collected for mRNA sequencing. The experiment was run in triplicates.