Tumour vasculature at single-cell resolution

Xu Pan, Xin Li, Liang Dong, Teng Liu, Min Zhang, Lining Zhang, Xiyuan Zhang, Lingjuan Huang, Wensheng Shi, Hongyin Sun, Zhaoyu Fang, Jie Sun, Yaoxuan Huang, Hua Shao, Yeqi Wang and Mingzhu Yin ()
Additional contact information
Xu Pan: Chongqing University
Xin Li: Chongqing University
Liang Dong: Central South University
Teng Liu: Chongqing University
Min Zhang: Central South University
Lining Zhang: Chongqing University
Xiyuan Zhang: Central South University
Lingjuan Huang: Central South University
Wensheng Shi: Central South University
Hongyin Sun: Chongqing University
Zhaoyu Fang: School of Computer Science and Engineering at Central South University
Jie Sun: Chongqing University
Yaoxuan Huang: Chongqing University
Hua Shao: Chongqing University
Yeqi Wang: Bioengineering College of Chongqing University
Mingzhu Yin: Chongqing University

Nature, 2024, vol. 632, issue 8024, 429-436

Abstract: Abstract Tumours can obtain nutrients and oxygen required to progress and metastasize through the blood supply1. Inducing angiogenesis involves the sprouting of established vessel beds and their maturation into an organized network2,3. 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+ tip cells at the SI stage (APLN+ TipSI) advanced to TipSIII 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+ TipSI 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+ 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.

Date: 2024
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DOI: 10.1038/s41586-024-07698-1

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