Single-cell transcriptomic analyses reveal distinct dorsal/ventral pancreatic programs

The pancreas of vertebrates is separately derived from both the dorsal and ventral endodermal domains. However, the difference between these two programs has been unclear. Here, using a pancreatic determination gene, Pdx1, driven GFP transgenic mouse strain, we identified Pdx1-GFP highly expressing cells (Pdx1^high) and Pdx1-GFP lowly expressing cells (Pdx1^low) in both embryonic dorsal Pdx1-expressing region (DPR) and ventral Pdx1-expressing region (VPR). We analyzed the transcriptomes of single Pdx1^low and Pdx1^high cells from the DPR and VPR. In the VPR, Pdx1^low cells have an intermediate progenitor identity and can generate hepatoblasts, extrahepatobiliary cells, and Pdx1^high pancreatic progenitor cells. In the DPR, Pdx1^high cells are directly specified as pancreatic progenitors, whereas Pdx1^low cells are precocious endocrine cells. Therefore, our study defines distinct road maps for dorsal and ventral pancreatic progenitor specification. The findings provide guidance for optimization of current β-cell induction protocols by following the in vivo dorsal pancreatic specification program.