在单细胞分辨率下瘤血管
Xu Pan1,2,3, Xin Li1,4,5, Liang Dong6
1Clinical Research Center (CRC), Medical Pathology Center (MPC), Cancer Early Detection and Treatment Center (CEDTC) and Translational Medicine Research Center (TMRC), Chongqing University Three Gorges Hospital, Chongqing University, Chongqing, China.
这项研究以单细胞分辨率绘制瘤血管图,揭示了血管如何形成,并表明APLN+ Tip细胞可能预测抗VEGF治疗反应.
科学领域:
- 癌症学
- 血管生物学
- 单细胞基因组学
背景情况:
- 瘤的生长和转移取决于血液供应和血管生成.
- 了解瘤血管结构对于开发抗血管生成疗法至关重要.
研究的目的:
- 在不同类型的癌症中创建全面的单细胞瘤血管图谱.
- 阐明瘤新血管化的细胞动态和通信.
- 确定疾病进展和治疗反应的潜在生物标志物.
主要方法:
- 来自31种癌症类型的372个捐赠者的约20万个单细胞RNA测序.
- 对血管细胞分化途径的导向推断.
- 细胞间通信分析以了解微环境的相互作用.
主要成果:
- 瘤血管生成从静脉内皮细胞开始,并向动脉化发展.
- APLN+Tip细胞 (APLN+TipSI) 和它们向TipSIII细胞的过渡涉及Notch信号.
- 干细胞与化学因子和TEK表达的变化发生差异化.
- APLN+ TipSI细胞与疾病进展相关,并预测抗VEGF治疗的反应.
- 在淋巴血管生成和抗原呈现方面发现了不同的淋巴内皮细胞系.
- 细胞内膜网应激与亲血管性BASP1+矩阵的产生有关.
- 新血管内皮细胞有助于免疫抑制瘤微环境.
结论:
- 在单细胞分辨率下提供前所未有的细节.
- APLN+ TipSI细胞是预测抗VEGF治疗结果的有希望的生物标志物.
- 这些发现对抗血管新生疗法的临床应用有重大影响.
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