【文献速览】-Spatial transcriptomics r

During tumor progression, cancer cells come into contact with new cell types in the microenvironment, but it is unclear how tumor cells adapt to new environments. Here, we integrate spatial transcriptomics and scRNA-seq to characterize tumor/microenvironment interactions during the initial steps of invasion. Using a zebrafish model of melanoma, we identify a unique “interface” cell state at the tumor/microenvironment boundary. This interface is composed of specialized tumor and microenvironment cells that upregulate a common set of cilia genes, and cilia proteins are enriched only where the tumor contacts the microenvironment. Cilia gene expression is regulated by ETS-family transcription factors, which normally act to suppress cilia genes outside of the interface. An ETS-driven interface is conserved across ten patient samples, suggesting it is a conserved feature of human melanoma. Our results demonstrate the power of spatial transcriptomic approaches in uncovering mechanisms that allow tumors to invade into the microenvironment.

在肿瘤发展过程中，肿瘤细胞在微环境中接触到新的细胞类型，但肿瘤细胞如何适应新环境尚不清楚。在这里，我们整合了空间转录组学和scRNA-seq来表征肿瘤/微环境在侵袭初始阶段的相互作用。利用黑素瘤的斑马鱼模型，我们在肿瘤/微环境边界识别了一种独特的界面细胞状态。该界面由肿瘤和微环境细胞组成，这些细胞上调一组共同的纤毛基因，而纤毛蛋白只有在肿瘤接触微环境的地方才富集。纤毛基因的表达受ETS家族转录因子的调控，其作用通常是在界面外抑制纤毛基因。ETS驱动的界面在10个患者样本中是保守的，表明它是人类黑色素瘤的保守特征。我们的结果证明了空间转录组学方法在揭示允许肿瘤侵入微环境的机制方面的力量。