Time course analysis of the effect of reseeding on laminin-411 vs fibronectin on gene expression in in vitro differentiated pancreatic progenitor cells.

The extracellular matrix has recently emerged as a key regulator of endocrine fate choice in the pancreas via integrins and YAP signaling. To elucidate the intermediate mechanism between exposure to specific ECM components and induction of a proendocrine transcriptional program, we performed bulk RNA sequencing of in vitro differentiated HUES4-derived pancreatic progenitor cells. Cells were reseeded on either fibronectin (FN, non-endocrinogenic) or laminin-411 (LN411, highly endocrinogenic) and RNA was collected after 3, 6, or 24 hours. The dataset revealed a progressive induction of an endocrinogenic program, but with significant upregulation of endocrine genes only at the 24 hour time point. Interestingly, other YAP target genes were strongly and significantly downregulated already at 6 hours. Additionally, the dataset revealed novel potential intermediate regulators between LN411-exposure, YAP inhibition and endocrine specification. Overall design: To investigate the intermediate effects between exposure to laminin-411 and endocrine fate choice, ESC-derived pancreatic progenitor cells were reseeded on either laminin-411 or fibronectin and harvested after 3, 6, or 24 hours. Triplicates were collected and sequenced for each condition.