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 (Pdx1high) and Pdx1-GFP lowly expressing cells (Pdx1low) in both embryonic dorsal Pdx1-expressing region (DPR) and ventral Pdx1-expressing region (VPR). We analyzed the transcriptomes of single Pdx1low and Pdx1high cells from the DPR and VPR. In the VPR, Pdx1low cells have an intermediate progenitor identity and can generate hepatoblasts, extrahepatobiliary cells, and Pdx1high pancreatic progenitor cells. In the DPR, Pdx1high cells are directly specified as pancreatic progenitors, whereas Pdx1low 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 ß-cell induction protocols by following the in vivo dorsal pancreatic specification program. Overall design: The overall goal of this study was understanding the programs of ventral and dorsal pancreatic progenitor development. Specifically, to get an overall gene expression profiles during ventral and dorsal pancreas development, we performed bulk cell RNA-seq in E10.5 ventral and dorsal pancreatic progenitor cells purified from Pdx1-GFP transgene embryos; E14.5 ventral and dorsal endocrine progenitor cells from Ngn3-GFP transgene embryos; and E17.5 ventral and dorsal beta cells from Insulin-RFP transgene embryos. To determine the progress and cell type components during the specification of pancreatic progenitor in ventral and dorsal domains, we performed single-cell transcriptomic analysis in sorted Pdx1-GFP+ cells from ventral and dorsal pancreatic buds.

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Li LC, Qiu WL, Zhang YW, Xu ZR, Xiao YN, Hou C, Lamaoqiezhong, Yu P, Cheng X, Xu CR