TrxG complex catalytic and non-catalytic activity play distinct roles in pancreas progenitor specification and differentiation (E18.5 Dpy30?P pancreas)

Purpose: To gain insight into why Dpy30?P acinar cells fail to express terminal makers, we performed RNA-seq using E18.5 control and Dpy30?P pancreata. Methods: Floxed Dpy30 mice were crossed to Pdx1-Cre driver mice to obtain conditional deletion of Dpy30 exon 4 in the pancreas. In all studies, knockout mice (Dpy30?P, Pdx1-Cre; Dpy30flox/flox) were compared to littermate controls (Dpy30flox/flox or Dpy30flox/wt). Results: Differential gene expression analysis demonstrated that endocrine cell hormones such as Ins2 and acinar cell digestive enzymes were downregulated in the E18.5 Dpy30?P pancreas compared to controls. GO term analysis indicated that genes involved in pancreatic secretion, digestion and proteolysis were reduced in Dpy30?P cells. Notably, transcripts with very high expression levels (above 9000 FPKM) were more downregulated in the E18.5 Dpy30?P pancreas compared to transcripts with lower expression levels. Conclusions: Overall, these data suggest increased variation in acinar cell transcript expression in the Dpy30?P pancreas. Overall design: Single-cell RNA-sequencing was performed using one E18.5 control and one E18.5 Dpy30?P pancreas