Early Human Pancreas Cell Study

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Summary

Using third-person perspective, the team studied early human pancreas development to uncover insights for pancreatic ailment treatments. Through extensive single-cell analysis on embryonic pancreas tissue from first-trimester embryos, they discerned the diverse molecular characteristics, developmental paths, and controlling networks of primary cell kinds. Their research revealed that in humans, dorsal pancreatic cells show varied gene expressions compared to their ventral counterparts. They pinpointed the progenitors producing ventral cells and discovered that mesenchymal cell-derived Notch and MAPK signals guide multipotent cell differentiation. Interestingly, they spotted endocrine progenitor groups with varied differentiation capacities. While many developmental paths mirrored those in mice, unique gene expression variations emerged. This work offers a detailed view of early pancreatic growth, emphasizing its intricate molecular and lineage shifts.

Research Criteria

The article focuses on understanding the molecular heterogeneity, developmental trajectory, and regulatory network of early human pancreas development. The study aims to depict the progression of pancreatic organogenesis during the first trimester at the single-cell level.

Fig.1 Experimental design¹.

Sample Type

Early human pancreas.

Result—Cell Diversity of the Human Pancreas in Early Development

In an intricate exploration of human pancreatic development during its embryonic phase, researchers meticulously examined pancreas samples from 17 donors, spanning 8 distinct developmental time points from the 4th to the 11th post-conception week (PCW). Utilizing the advanced 10x Genomics platform for single-cell RNA sequencing (scRNA-seq), they discerned a rich tapestry of cellular diversity, identifying six predominant cell classes: epithelial, mesenchymal, endothelial, neural, immune, and erythroid. Notably, the mesenchymal cells, which predominated in the early stages, witnessed a decline in their proportion from PCW 7 to 11, giving way to an upsurge in epithelial and other cell types. This dynamic cellular landscape underscores the intricate orchestration of cellular differentiation and proliferation during the nascent stages of pancreatic development.

Fig.2 Major cell types in the early human fetal pancreatic epithelium were identified using scRNA-seq¹.

Result—Profiling of the Developing Human Pancreatic Using scATAC-seq

In a meticulous exploration of the gene regulatory mechanisms steering pancreatic lineage differentiation, researchers employed scATAC-seq profiling on human embryonic pancreas tissues from PCW 8-11. This comprehensive analysis yielded 12,288 cells post quality control, revealing major cell classes that harmonized with prior scRNA-seq findings. Delving deeper into the pancreatic epithelium differentiation, the study discerned cell types across acinar, ductal, and endocrine lineages. A captivating observation emerged: specific cell populations, notably acinar, duct EP, and endocrine cells, manifested in the scATAC-seq data prior to their appearance in the scRNA-seq. This suggests that gene regulation might precede actual gene expression. Pseudotime evaluations mirrored trajectories seen in scRNA-seq, underscoring the congruence between the two profiles. Furthermore, mature acinar and endocrine lineage cells exhibited a pronounced number of distinct peaks, potentially indicative of their advanced maturity and the evolution of intricate functions.

Fig.3 scATAC-seq of pancreatic epithelial cells¹.

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Reference

1. Ma, Zhuo, et al. "Deciphering early human pancreas development at the single-cell level." Nature Communications 14.1 (2023): 5354.