Back to Search
Start Over
Tumour vasculature at single-cell resolution.
- Source :
-
Nature [Nature] 2024 Aug; Vol. 632 (8024), pp. 429-436. Date of Electronic Publication: 2024 Jul 10. - Publication Year :
- 2024
-
Abstract
- Tumours can obtain nutrients and oxygen required to progress and metastasize through the blood supply <superscript>1</superscript> . Inducing angiogenesis involves the sprouting of established vessel beds and their maturation into an organized network <superscript>2,3</superscript> . Here we generate a comprehensive atlas of tumour vasculature at single-cell resolution, encompassing approximately 200,000 cells from 372 donors representing 31 cancer types. Trajectory inference suggested that tumour angiogenesis was initiated from venous endothelial cells and extended towards arterial endothelial cells. As neovascularization elongates (through angiogenic stages SI, SII and SIII), APLN <superscript>+</superscript> tip cells at the SI stage (APLN <superscript>+</superscript> Tip <superscript>SI</superscript> ) advanced to Tip <superscript>SIII</superscript> cells with increased Notch signalling. Meanwhile, stalk cells, following tip cells, transitioned from high chemokine expression to elevated TEK (also known as Tie2) expression. Moreover, APLN <superscript>+</superscript> Tip <superscript>SI</superscript> cells not only were associated with disease progression and poor prognosis but also hold promise for predicting response to anti-VEGF therapy. Lymphatic endothelial cells demonstrated two distinct differentiation lineages: one responsible for lymphangiogenesis and the other involved in antigen presentation. In pericytes, endoplasmic reticulum stress was associated with the proangiogenic BASP1 <superscript>+</superscript> matrix-producing pericytes. Furthermore, intercellular communication analysis showed that neovascular endothelial cells could shape an immunosuppressive microenvironment conducive to angiogenesis. This study depicts the complexity of tumour vasculature and has potential clinical significance for anti-angiogenic therapy.<br /> (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
- Subjects :
- Humans
Antigen Presentation
Cell Communication
Cell Differentiation
Cell Lineage
Disease Progression
Endoplasmic Reticulum Stress
Lymphangiogenesis
Pericytes pathology
Pericytes cytology
Pericytes metabolism
Prognosis
Receptors, Notch metabolism
Signal Transduction
Tumor Microenvironment
Vascular Endothelial Growth Factor A antagonists & inhibitors
Animals
Zebrafish
Endothelial Cells cytology
Endothelial Cells immunology
Endothelial Cells metabolism
Neoplasms blood supply
Neoplasms classification
Neoplasms drug therapy
Neoplasms pathology
Neovascularization, Pathologic pathology
Single-Cell Analysis
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 632
- Issue :
- 8024
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 38987599
- Full Text :
- https://doi.org/10.1038/s41586-024-07698-1