Single-Cell Meta-Analysis Uncovers the Pancreatic Endothelial Cell Transcriptomic Signature and Reveals a Key Role...

Area of Science:

• Vascular Biology
• Endocrinology
• Genomics

Background:

• Pancreatic vasculature has unique adaptations for insulin response.
• Digestive enzymes hinder pancreatic endothelial cell (EC) characterization, limiting understanding of EC specialization.

Purpose of the Study:

• To identify pancreatic EC-specific genes and create an integrated human pancreatic EC atlas.
• To elucidate the role of transcription factors in pancreatic EC specialization.

Main Methods:

• Analysis of single-nuclei/single-cell RNA-sequencing data to identify EC-enriched genes.
• Validation using bulk RNA-sequencing, spatial transcriptomics, immunofluorescence, and RNAScope.
• Functional validation of NKX2-3 in human umbilical vein endothelial cells (HUVECs).

Main Results:

• Defined a conserved pancreatic EC-enriched gene signature involved in ECM, barrier function, and signaling pathways.
• Identified a specialized islet capillary subpopulation with unique gene expression profiles.
• Discovered NKX2-3 as a key transcription factor regulating pancreatic EC-enriched genes, including PLVAP and SPARCL1.

Conclusions:

• A validated transcriptomic signature for pancreatic ECs was established, highlighting their heterogeneity.
• NKX2-3 was identified as a critical regulator of pancreatic EC gene expression.
• An online resource for exploring pancreatic endothelial cell data was created.