Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Beijing, China.
PKU-Tsinghua-NIBS Graduate Program, Peking University, Beijing, China.
EMBO Rep. 2018 Oct;19(10). doi: 10.15252/embr.201846148. Epub 2018 Jul 31.
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, , driven GFP transgenic mouse strain, we identified Pdx1-GFP highly expressing cells (Pdx1) and Pdx1-GFP lowly expressing cells (Pdx1) in both embryonic dorsal Pdx1-expressing region (DPR) and ventral Pdx1-expressing region (VPR). We analyzed the transcriptomes of single Pdx1 and Pdx1 cells from the DPR and VPR. In the VPR, Pdx1 cells have an intermediate progenitor identity and can generate hepatoblasts, extrahepatobiliary cells, and Pdx1 pancreatic progenitor cells. In the DPR, Pdx1 cells are directly specified as pancreatic progenitors, whereas Pdx1 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 dorsal pancreatic specification program.
脊椎动物的胰腺分别由背侧和腹侧内胚层区域衍生而来。然而，这两个程序之间的差异尚不清楚。在这里，我们使用一个胰腺决定基因 ， 驱动 GFP 转基因小鼠品系，在胚胎背侧 Pdx1 表达区域 (DPR) 和腹侧 Pdx1 表达区域 (VPR) 中，我们鉴定了 Pdx1-GFP 高表达细胞 (Pdx1) 和 Pdx1-GFP 低表达细胞 (Pdx1)。我们分析了来自 DPR 和 VPR 的单个 Pdx1 和 Pdx1 细胞的转录组。在 VPR 中，Pdx1 细胞具有中间祖细胞特征，可以产生肝母细胞、肝胆外细胞和 Pdx1 胰腺祖细胞。在 DPR 中，Pdx1 细胞直接被指定为胰腺祖细胞，而 Pdx1 细胞则是早熟的内分泌细胞。因此，我们的研究为背侧和腹侧胰腺祖细胞的特化定义了不同的路线图。这些发现为通过遵循背侧胰腺特化程序优化当前的 β 细胞诱导方案提供了指导。
