In the first pan-cancer analysis of the tumor vasculature, Pan and colleagues profile nearly 200,000 endothelial and mural cells (ECs and MCs), identifying novel subclusters and cell states using consensus trajectory inference. They identify differentiation trajectories in vascular and lymphatic endothelial cells, and subtype the pericyte population. During sprouting angiogenesis, venous cells dedifferentiate and transition to capillary and, finally, arterial ECs. Capillary ECs transition via “three angiogenic stages” (SI-SIII) during which APLN+ TipS1 cells were identified as potential modulators of tumor-induced neovascularization and anti-angiogenic therapy response. In lymphatic ECs, differentiation was inversely correlated between the lymphangiogenic (T1) and antigen-presenting (T2) trajectories, with T2 associated with a better prognosis. While several pericyte clusters were identified, BASP1+ matrix-associated pericytes were associated with APLN+ TipS1 cells and had a worse prognosis. These findings present transcriptional validation of previous experimental findings and serve as a resource to examine the tumor vascular microenvironment in detail.

中文翻译：

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转录组放大镜下的泛肿瘤脉管系统


在肿瘤脉管系统的首次泛癌分析中，Pan 及其同事分析了近 200,000 个内皮细胞和壁细胞（ECs 和 MCs），使用共识轨迹推断识别了新的亚簇和细胞状态。它们识别血管和淋巴内皮细胞中的分化轨迹，并对周细胞群进行亚型分析。在发芽血管生成过程中，静脉细胞去分化并转变为毛细血管，最后转化为动脉 EC。毛细血管 ECs 通过“三个血管生成阶段”（SI-SIII） 进行转换，在此期间，APLN+ TipS1 细胞被确定为肿瘤诱导的新血管形成和抗血管生成治疗反应的潜在调节剂。在淋巴 ECs 中，淋巴管生成 （T1） 和抗原呈递 （T2） 轨迹之间的分化呈负相关，T2 与较好的预后相关。虽然鉴定出几个周细胞簇，但 BASP1 + 基质相关周细胞与 APLN+ TipS1 细胞相关，预后较差。这些发现提供了对先前实验结果的转录验证，并作为详细检查肿瘤血管微环境的资源。