Gene Expression Profiling of the Mouse Pancreas during the Secondary Transition in the Organogenesis of the Pancreatic Gland*

Abstract

Diabetes mellitus is a chronic disease that \nimpacts the homeostasis of blood sugar levels caused by loss or defect of \ninsulin-producing β-cells in the Islets of Langerhans. Type 1 diabetes (T1D) is caused by auto-immune mediated\xa0destruction of \nβ-cells, whereas in T2D, insulin is produced but used inefficiently. T2D accounts for 90% of people with diabetes worldwide (WHO 1999) and is the fastest increasing disease worldwide (https://diabetesatlas.org/en/). For an improved understanding of the pathomechanism of \ndiabetes, profound knowledge of pancreas organogenesis and the associated gene \nregulatory networks is required. Therefore, we dissected and profiled the \npancreatic endodermal and non-endodermal compartment between the embryonic \nstages (E) 12.5 and E 15.5 when progenitor cells commit to their different \npancreatic lineages. Our associated study mined the global mRNA expression \nprofile to increase the understanding of the secondary transition, \nendodermal-non-endodermal tissue interaction, and diabetic-related gene \nregulation. Furthermore, we validated 635 regulated pancreatic genes using the \npublicly available GenePaint.org, \nrespective gp3.mpg.de to evaluate genes associated with genetic variants in \nSingle-nucleotide polymorphism (SNP) related to T2D.