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单细胞多阶段的空间进化,食道癌发生的进化地图
Jiang Chang1, Junting Lu2, Qingyi Liu2
1Department of Health Toxicology, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
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概括
癌症的进展涉及细胞和微环境的共同进化. 一个空间地图揭示了一个特定的细胞类型破坏组织屏障和招募纤维细胞,形成一个保护瘤和影响食道状细胞癌患者的结果的利基.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
背景情况:
- 癌症的发展是恶性细胞及其微观环境之间的复杂相互作用.
- 了解这种相互作用的空间动态对于破译癌症进展至关重要.
- 瘤微环境中的物理架构和细胞通信仍然不太清楚.
研究的目的:
- 创建人类食道状细胞癌 (ESCC) 的高分辨率空间转录基因地图.
- 为了绘制癌细胞在其微观环境中的进化轨迹.
- 确定驱动ESCC进展的关键细胞相互作用及其临床影响.
主要方法:
- 在单细胞分辨率的空间转录组学.
- 分析了来自43名ESCC患者的127个多阶段视野.
- 绘制了超过640万个细胞的进化路径.
主要成果:
- 鉴定出一种促使ESCC进展的增殖性上皮细胞亚群.
- 证明这些细胞获得了无差异化和侵入性特征.
- 在癌前阶段通过JAG1-NOTCH1信号向癌症相关纤维细胞 (CAFs) 招募正常纤维细胞.
- 在瘤边缘发现了保护性"CAF-Epi"的形成,防止免疫监视.
结论:
- CAF-Epi利基形成是ESCC进展的关键指标,并影响患者的治疗结果.
- 这种机制不仅在ESCC中,而且在其他状细胞癌中也很重要.
- 空间绘图为癌症演变和微环境相互作用提供了关键的见解.
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