Single-cell atlas of human pancreatic islet and acinar endothelial cells in health and diabetes
Abstract 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...
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55415-3 |
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| author | Rebecca Craig-Schapiro Ge Li Kevin Chen Jesus M. Gomez-Salinero Ryan Nachman Aleksandra Kopacz Ryan Schreiner Xiaojuan Chen Qiao Zhou Shahin Rafii David Redmond |
| author_facet | Rebecca Craig-Schapiro Ge Li Kevin Chen Jesus M. Gomez-Salinero Ryan Nachman Aleksandra Kopacz Ryan Schreiner Xiaojuan Chen Qiao Zhou Shahin Rafii David Redmond |
| author_sort | Rebecca Craig-Schapiro |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-287af39183974606a03715fa7cad2fe6 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-287af39183974606a03715fa7cad2fe62025-02-09T12:45:27ZengNature PortfolioNature Communications2041-17232025-02-0116111910.1038/s41467-024-55415-3Single-cell atlas of human pancreatic islet and acinar endothelial cells in health and diabetesRebecca Craig-Schapiro0Ge Li1Kevin Chen2Jesus M. Gomez-Salinero3Ryan Nachman4Aleksandra Kopacz5Ryan Schreiner6Xiaojuan Chen7Qiao Zhou8Shahin Rafii9David Redmond10Division of Transplant Surgery, Weill Cornell MedicineHartman Institute for Therapeutic Organ Regeneration, Division of Regenerative Medicine, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell MedicineHartman Institute for Therapeutic Organ Regeneration, Division of Regenerative Medicine, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell MedicineHartman Institute for Therapeutic Organ Regeneration, Division of Regenerative Medicine, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell MedicineHartman Institute for Therapeutic Organ Regeneration, Division of Regenerative Medicine, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell MedicineHartman Institute for Therapeutic Organ Regeneration, Division of Regenerative Medicine, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell MedicineHartman Institute for Therapeutic Organ Regeneration, Division of Regenerative Medicine, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell MedicineColumbia Center for Translational Immunology, Department of Surgery, Columbia University Medical CenterHartman Institute for Therapeutic Organ Regeneration, Division of Regenerative Medicine, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell MedicineHartman Institute for Therapeutic Organ Regeneration, Division of Regenerative Medicine, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell MedicineHartman Institute for Therapeutic Organ Regeneration, Division of Regenerative Medicine, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell MedicineAbstract 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.https://doi.org/10.1038/s41467-024-55415-3 |
| spellingShingle | Rebecca Craig-Schapiro Ge Li Kevin Chen Jesus M. Gomez-Salinero Ryan Nachman Aleksandra Kopacz Ryan Schreiner Xiaojuan Chen Qiao Zhou Shahin Rafii David Redmond Single-cell atlas of human pancreatic islet and acinar endothelial cells in health and diabetes Nature Communications |
| title | Single-cell atlas of human pancreatic islet and acinar endothelial cells in health and diabetes |
| title_full | Single-cell atlas of human pancreatic islet and acinar endothelial cells in health and diabetes |
| title_fullStr | Single-cell atlas of human pancreatic islet and acinar endothelial cells in health and diabetes |
| title_full_unstemmed | Single-cell atlas of human pancreatic islet and acinar endothelial cells in health and diabetes |
| title_short | Single-cell atlas of human pancreatic islet and acinar endothelial cells in health and diabetes |
| title_sort | single cell atlas of human pancreatic islet and acinar endothelial cells in health and diabetes |
| url | https://doi.org/10.1038/s41467-024-55415-3 |
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