Deciphering early human pancreas development at the single-cell level

Zhuo Ma, Xiaofei Zhang, Wen Zhong, Hongyan Yi, Xiaowei Chen, Yinsuo Zhao, Yanlin Ma (), Eli Song () and Tao Xu ()
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Zhuo Ma: Chinese Academy of Sciences
Xiaofei Zhang: Chinese Academy of Sciences
Wen Zhong: Linköping University
Hongyan Yi: The First Affiliated Hospital of Hainan Medical University, Hainan Medical University
Xiaowei Chen: Chinese Academy of Sciences
Yinsuo Zhao: Chinese Academy of Sciences
Yanlin Ma: The First Affiliated Hospital of Hainan Medical University, Hainan Medical University
Eli Song: Chinese Academy of Sciences
Tao Xu: Chinese Academy of Sciences

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Understanding pancreas development can provide clues for better treatments of pancreatic diseases. However, the molecular heterogeneity and developmental trajectory of the early human pancreas are poorly explored. Here, we performed large-scale single-cell RNA sequencing and single-cell assay for transposase accessible chromatin sequencing of human embryonic pancreas tissue obtained from first-trimester embryos. We unraveled the molecular heterogeneity, developmental trajectories and regulatory networks of the major cell types. The results reveal that dorsal pancreatic multipotent cells in humans exhibit different gene expression patterns than ventral multipotent cells. Pancreato-biliary progenitors that generate ventral multipotent cells in humans were identified. Notch and MAPK signals from mesenchymal cells regulate the differentiation of multipotent cells into trunk and duct cells. Notably, we identified endocrine progenitor subclusters with different differentiation potentials. Although the developmental trajectories are largely conserved between humans and mice, some distinct gene expression patterns have also been identified. Overall, we provide a comprehensive landscape of early human pancreas development to understand its lineage transitions and molecular complexity.

Date: 2023
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DOI: 10.1038/s41467-023-40893-8

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