Single cell transcriptional diversity and intercellular crosstalk of human liver cancer.
Single cell transcriptional diversity and intercellular crosstalk of human liver cancer.
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DOI：
10.1038/s41419-022-04689-w
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发表时间：
2022-03-24
影响因子：
9
通讯作者：
Wei L
中科院分区：
文献类型：
--
作者：
Meng Y;Sang Y;Liao J;Zhao Q;Qu S;Li R;Jiang J;Wang M;Wang J;Wu D;Cheng C;Wei L
肝癌起源于动态肿瘤微环境（TME）的进化选择，其中肿瘤细胞通常变得更加异质;然而，TME介导的肝癌转录多样性的机制仍不清楚。在这里，我们通过单细胞转录组分析评估15例肝癌患者的转录多样性，并观察肿瘤细胞的转录多样性与肝癌患者的干性相关。肿瘤相关成纤维细胞（TAF）作为肿瘤内和肿瘤间肿瘤细胞异质性背后的潜在驱动力，被预测通过COL 1A 1-ITGA 2与高度异质性肿瘤细胞相互作用。此外，COL 1A 1介导的YAP信号激活可能是TAF与具有增加的转录多样性的肿瘤细胞之间的机制联系。引人注目的是，COL 1A 1、ITGA 2和雅普的水平与肝癌患者的形态异质性和较差的总体存活率相关。除了提供TME和异质性肿瘤细胞之间的潜在机制联系外，本研究还确定胶原刺激的雅普激活通过上调干性与肿瘤细胞的转录多样性相关，为个体化治疗靶点提供了理论基础。
Liver cancer arises from the evolutionary selection of the dynamic tumor microenvironment (TME), in which the tumor cell generally becomes more heterogeneous; however, the mechanisms of TME-mediated transcriptional diversity of liver cancer remain unclear. Here, we assess transcriptional diversity in 15 liver cancer patients by single-cell transcriptome analysis and observe transcriptional diversity of tumor cells is associated with stemness in liver cancer patients. Tumor-associated fibroblast (TAF), as a potential driving force behind the heterogeneity in tumor cells within and between tumors, was predicted to interact with high heterogeneous tumor cells via COL1A1-ITGA2. Moreover, COL1A1-mediated YAP-signaling activation might be the mechanistic link between TAF and tumor cells with increased transcriptional diversity. Strikingly, the levels of COL1A1, ITGA2, and YAP are associated with morphological heterogeneity and poor overall survival of liver cancer patients. Beyond providing a potential mechanistic link between the TME and heterogeneous tumor cells, this study establishes that collagen-stimulated YAP activation is associates with transcriptional diversity in tumor cells by upregulating stemness, providing a theoretical basis for individualized treatment targets.
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