GSE134182
TrxG complex catalytic and non-catalytic activity play distinct roles in pancreas progenitor specification and differentiation (shDpy30 lentivirus treated spheres)
Purpose: To determine the genome-wide effect of Wdr5 and Dpy30 suppression on acinar, duct and endocrine gene activation during pancreas spheroid differentiation Methods: We adapted an ex vivo mouse E13.5 pancreas spheroid model of growth and differentiation (Sugiyama et al., 2013) and generated RNA-sequencing data from pooled shScramble, shWdr5 and shDpy30 spheroids. Results: We identified 1,744 genes whose expression was substantially impaired and 693 genes with increased expression in shWdr5-treated spheres compared to shScramble controls. In shDpy30-treated spheres, we identified no genes with impaired expression and only 2 genes with increased expression compared to shScramble controls. Genes expressed in pancreas progenitors were largely not altered by either Wdr5 or Dpy30 suppression. However, genes expressed in the endocrine (Gcg, Ins1, Ins2 and Neurog3) and acinar (Cpa1, Cpa2 and Amy2) lineages had dramatically reduced expression in shWdr5-treated spheres, but were unaffected by Dpy30 suppression. Conclusions: These data suggest that the co-activator activity of the TrxG complexes and not their methyltransferase activity, is required for acinar and endocrine cell gene activation in an ex vivo model of pancreas development. Overall design: RNA-sequencing data was generated from combining > 4 sphere differentiations from Day 7 shScramble, shWdr5 and shDpy30 lentivirus treated spheres