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. Single-cell RNA-sequencing was performed using one E18.5 control and one E18.5 Dpy30∆P pancreas