GSE134181
TrxG complex catalytic and non-catalytic activity play distinct roles in pancreas progenitor specification and differentiation (E18.5 Dpy30?P pancreas scRNA-seq)
Purpose: To gain insight into why Dpy30?P acinar cells fail to express terminal makers, we performed scRNA-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: In total, we sequenced 8,050 control and 7,858 Dpy30?P cells that with the E13.5 scRNA-seq data allowed us to identify 2,207 control and 2,354 Dpy30?P epithelial cells. We found a cluster that contained almost entirely Dpy30?P cells, where the expression of acinar cell digestive enzymes was consistently low. The distribution of gene expression values for terminal acinar markers suggested an increased distribution in gene expression levels in the Dpy30?P cells relative to control cells; however, this was not the case for terminal endocrine markers. Comparing the variance-to-mean ratios in the Dpy30?P and control cells showed an increase in variance in the Dpy30?P acinar cells but not in endocrine cells. 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