Craig-Schapiro Rebecca, Li Ge, Chen Kevin, Gomez-Salinero Jesus M, Nachman Ryan, Kopacz Aleksandra, Schreiner Ryan, Chen Xiaojuan, Zhou Qiao, Rafii Shahin, Redmond David
Division of Transplant Surgery, Weill Cornell Medicine, New York, NY, USA.
Hartman Institute for Therapeutic Organ Regeneration, Division of Regenerative Medicine, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Nat Commun. 2025 Feb 6;16(1):1338. doi: 10.1038/s41467-024-55415-3.
Characterization of the vascular heterogeneity within the pancreas has previously been lacking. Here, we develop strategies to enrich islet-specific endothelial cells (ISECs) and acinar-specific endothelial cells (ASECs) from three human pancreases and corroborate these findings with three published pancreatic datasets. Single-cell RNA sequencing reveals the unique molecular signatures of ISECs, including structural genes COL13A1, ESM1, PLVAP, UNC5B, and LAMA4, angiocrine genes KDR, THBS1, BMPs and CXCR4, and metabolic genes ACE, PASK and F2RL3. ASECs display distinct signatures including GPIHBP1, CCL14, CD74, AQP1, KLF4, and KLF2, which may manage the inflammatory and metabolic needs of the exocrine pancreas. Ligand-receptor analysis suggests ISECs and ASECs interact with LUM fibroblasts and RGS5 pericytes and smooth muscle cells via VEGF-A:VEGFR2, CXCL12:CXCR4, and LIF:LIFR pathways. Comparative expression and immunohistochemistry indicate disruption of endothelial-expressed CD74, ESM1, PLVAP, THBD, VWA1, and VEGF-A cross-talk among vascular and other cell types in diabetes. Thus, our data provide a single-cell vascular atlas of human pancreas, enabling deeper understanding of pancreatic pathophysiology in health and disease.
胰腺内血管异质性的特征此前一直缺乏。在此，我们开发了从三个人类胰腺中富集胰岛特异性内皮细胞（ISEC）和腺泡特异性内皮细胞（ASEC）的策略，并用三个已发表的胰腺数据集证实了这些发现。单细胞RNA测序揭示了ISEC的独特分子特征，包括结构基因COL13A1、ESM1、PLVAP、UNC5B和LAMA4，血管分泌基因KDR、THBS1、骨形态发生蛋白（BMP）和CXCR4，以及代谢基因ACE、PASK和F2RL3。ASEC表现出不同的特征，包括GPIHBP1、CCL14、CD74、水通道蛋白1（AQP1）、KLF4和KLF2，它们可能调节外分泌胰腺的炎症和代谢需求。配体-受体分析表明，ISEC和ASEC通过VEGF-A:VEGFR2、CXCL12:CXCR4和LIF:LIFR途径与LUM成纤维细胞以及RGS5周细胞和平滑肌细胞相互作用。比较性表达和免疫组化表明，糖尿病中血管和其他细胞类型之间内皮表达的CD74、ESM1、PLVAP、THBD、VWA1和VEGF-A的相互作用受到破坏。因此，我们的数据提供了人类胰腺的单细胞血管图谱，有助于更深入地了解健康和疾病状态下的胰腺病理生理学。
