比利时Vib-KULeuven癌症生物学中心Peter Carmeliet、深圳华大基因罗永伦、中山大学李旭日团队等合作，利用一种综合的基因表达谱分析方法,确定肺肿瘤内皮细胞的异质性和血管生成的候选物。这一研究成果2020年1月13日发表在国际学术期刊《癌细胞》上。

研究人员对人/小鼠（周）肿瘤肺和培养的人肺肿瘤内皮细胞（TECs）的56,771内皮细胞进行了单细胞RNA（scRNA）测序，并检测到17种已知和16种未知的表型，包括TECs可能调控免疫监视。研究人员将典型的尖端TECs分解为已知的迁移尖端和假定的基底膜破裂重塑表型。尖端TEC信号与患者的生存率相关，尖端/破裂TEC对血管内皮生长因子的阻断最为敏感。只有尖端TECs在物种/模型之间是一致的，并且有保守的标记。研究人员通过功能验证了scRNA测序数据与正交多组学和跨人群肿瘤荟萃分析数据的综合分析结果，并揭示了胶原蛋白修饰是候选的血管生成途径。

研究人员表示，单细胞水平揭示患者之间、物种（人/小鼠）和模型（体内/体外）肺肿瘤内皮细胞表型异质性的数据仍存有不足。

附：英文原文

Title: An Integrated Gene Expression Landscape Profiling Approach to Identify Lung Tumor Endothelial Cell Heterogeneity and Angiogenic Candidates

Author: Jermaine Goveia, Katerina Rohlenova, Federico Taverna, Lucas Treps, Lena-Christin Conradi, Andreas Pircher, Vincent Geldhof, Laura P.M.H. de Rooij, Joanna Kalucka, Liliana Sokol, Melissa García-Caballero, Yingfeng Zheng, Junbin Qian, Laure-Anne Teuwen, Shawez Khan, Bram Boeckx, Els Wauters, Herbert Decaluwé, Paul De Leyn, Johan Vansteenkiste, Birgit Weynand, Xavier Sagaert, Erik Verbeken, Albert Wolthuis, Baki Topal, Wouter Everaert, Hanibal Bohnenberger, Alexander Emmert, Dena Panovska, Frederik De Smet, Frank J.T. Staal, Rene J. Mclaughlin, Francis Impens, Vincenzo Lagani, Stefan Vinckier, Massimiliano Mazzone, Luc Schoonjans, Mieke Dewerchin, Guy Eelen, Tobias K. Karakach, Huanming Yang, Jian Wang, Lars Bolund, Lin Lin, Bernard Thienpont, Xuri Li, Diether Lambrechts, Yonglun Luo, Peter Carmeliet

Issue&Volume: 2020/01/13

Abstract: Heterogeneity of lung tumor endothelial cell (TEC) phenotypes across patients, species(human/mouse), and models (in vivo/in vitro) remains poorly inventoried at the single-cell level. We single-cell RNA (scRNA)-sequenced56,771 endothelial cells from human/mouse (peri)-tumoral lung and cultured human lungTECs, and detected 17 known and 16 previously unrecognized phenotypes, including TECsputatively regulating immune surveillance. We resolved the canonical tip TECs intoa known migratory tip and a putative basement-membrane remodeling breach phenotype. Tip TEC signatures correlated with patient survival, and tip/breach TECswere most sensitive to vascular endothelial growth factor blockade. Only tip TECswere congruent across species/models and shared conserved markers. Integrated analysisof the scRNA-sequenced data with orthogonal multi-omics and meta-analysis data acrossdifferent human tumors, validated by functional analysis, identified collagen modificationas a candidate angiogenic pathway.

DOI: 10.1016/j.ccell.2019.12.001

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(19)30571-9