GSE123759
RNA-seq Analysis of Pancreatic Epithelium and Mesenchyme from Wild Type and Pbx-mutant Embryos
The surrounding microenvironment plays a crucial role in pancreas formation and differentiation. Nevertheless, its cellular composition has not been analyzed in depth and whether different cell populations exist within the mesenchyme of the developing pancreas is an open question. Similarly, the molecular mechanisms by which the mesenchyme coordinates and integrates various signaling pathways to stimulate epithelial pancreatic progenitor proliferation and differentiation remain elusive.   Here, we investigate the cell composition and molecular network in the pancreatic mesenchyme, which promote pancreas differentiation. Whole transcriptome analysis and functional experiments showed that PBX in the mesenchyme promotes endocrine differentiation non-cell autonomously, acting at two different levels in the epithelial-mesenchymal crosstalk: 1) the maintenance of BM integrity and ECM and 2) regulation of soluble molecules, including guidance cues.  In conclusion, this study has identified distinct pancreatic mesenchymal niches and dissected their different roles during pancreatic development. This knowledge will be useful to improve current differentiation strategies based on ECM and soluble factors to generate ß-cell equivalents from pluripotent cells for future cell replacement therapies of diabetes. Overall design: We performed sequencing-based expression profiling (RNA-Seq) of pancreatic epithelial and mesenchymal cells isolated from wild type (WT) and Pbx mutant mice at embryonic day (E) 12.5 and E14.5