重庆大学附属三峡医院印明柱团队近期取得重要工作进展，他们研究绘制了单细胞分辨率的肿瘤血管系统图谱。相关研究成果2024年7月10日在线发表于《自然》杂志上。

据介绍，肿瘤可以通过血液供应获得进展和转移所需的营养和氧气。诱导血管生成涉及已建立的血管床的出芽及其成熟为有组织的网络。

研究人员以单细胞分辨率生成了肿瘤血管系统的综合图谱，包括来自372个供体的约20万个细胞，代表31种癌症类型。轨迹推断表明，肿瘤血管生成始于静脉内皮细胞，并向动脉内皮细胞延伸。随着新生血管的延长（通过血管生成阶段SI、SII和SIII），处于SI阶段的APLN⁺尖端细胞（APLN+Tip^SI）向Tip^SIII细胞发展，Notch信号传导增加。与此同时，茎细胞，继尖端细胞之后，从高趋化因子表达转变为TEK（也称为Tie2）表达升高。

此外，APLN⁺ Tip^SI细胞不仅与疾病进展和预后不良有关，而且有望预测对抗VEGF治疗的反应。淋巴管内皮细胞显示出两种不同的分化谱系：一种负责淋巴管生成，另一种参与抗原呈递。在周细胞中，内质网应激与促血管生成的BASP1⁺基质产生周细胞有关。不仅如此，细胞间通讯分析表明，新生血管内皮细胞可以形成有利于血管生成的免疫抑制微环境。

总之，本研究描述了肿瘤血管系统的复杂性，对抗血管生成治疗具有潜在的临床意义。

附：英文原文

Title: Tumour vasculature at single-cell resolution

Author: Pan, Xu, Li, Xin, Dong, Liang, Liu, Teng, Zhang, Min, Zhang, Lining, Zhang, Xiyuan, Huang, Lingjuan, Shi, Wensheng, Sun, Hongyin, Fang, Zhaoyu, Sun, Jie, Huang, Yaoxuan, Shao, Hua, Wang, Yeqi, Yin, Mingzhu

Issue&Volume: 2024-07-10

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.

DOI: 10.1038/s41586-024-07698-1

Source: https://www.nature.com/articles/s41586-024-07698-1