Deciphering early human pancreas development at the single-cell level

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. Here, the authors revealed molecular heterogeneity, developmental trajectory and regulatory network of early human pancreas development, and depict the whole progression of pancreatic organogenesis during the first trimester at the single-cell level.

Automated summary

In this study, the authors used single-cell RNA sequencing and single-cell assay for transposase accessible chromatin sequencing to explore the molecular heterogeneity, developmental trajectory, and regulatory networks of early human pancreas development. They identified differences in gene expression patterns between dorsal and ventral pancreatic multipotent cells in humans, and identified pancreato-biliary progenitors that generate ventral multipotent cells. Notch and MAPK signals from mesenchymal cells were found to regulate the differentiation of multipotent cells into trunk and duct cells. They also discovered different subclusters of endocrine progenitors with varying differentiation potentials. While the developmental trajectories were largely conserved between humans and mice, distinct gene expression patterns were also identified.