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EMBO Rep. 2018 Jul 31. pii: e46148. doi: 10.15252/embr.201846148. [Epub ahead of print]

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

Author information

1
Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Beijing, China.
2
PKU-Tsinghua-NIBS Graduate Program, Peking University, Beijing, China.
3
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
4
General Hospital of PLA Rocket Force, Beijing, China.
5
Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Beijing, China cxu@pku.edu.cn.

Abstract

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 β-cell induction protocols by following the in vivo dorsal pancreatic specification program.

KEYWORDS:

dorsal pancreas; fate map; single‐cell RNA‐seq; ventral pancreas

PMID:
30065074
DOI:
10.15252/embr.201846148

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