Malignant cell growth is fueled by interactions between tumor cells and the stromal cells composing the tumor microenvironment. The human liver is a major site of tumors and metastases, but molecular identities and intercellular interactions of different cell types have not been resolved in these pathologies. Here, we apply single cell RNA‐sequencing and spatial analysis of malignant and adjacent non‐malignant liver tissues from five patients with cholangiocarcinoma or liver metastases. We find that stromal cells exhibit recurring, patient‐independent expression programs, and reconstruct a ligand–receptor map that highlights recurring tumor–stroma interactions. By combining transcriptomics of laser‐capture microdissected regions, we reconstruct a zonation atlas of hepatocytes in the non‐malignant sites and characterize the spatial distribution of each cell type across the tumor microenvironment. Our analysis provides a resource for understanding human liver malignancies and may expose potential points of interventions.

中文翻译：

---

人肝肿瘤微环境的单细胞图谱

肿瘤细胞与构成肿瘤微环境的基质细胞之间的相互作用促进了恶性肿瘤细胞的生长。人类肝脏是肿瘤和转移的主要部位，但在这些病理中尚未解决不同细胞类型的分子特性和细胞间相互作用。在这里，我们对来自五名胆管癌或肝转移患者的恶性和邻近非恶性肝组织应用单细胞 RNA 测序和空间分析。我们发现基质细胞表现出重复的、独立于患者的表达程序，并重建配体-受体图谱，突出重复出现的肿瘤-基质相互作用。通过结合激光捕获显微切割区域的转录组学，我们重建了非恶性部位肝细胞的分区图谱，并表征了肿瘤微环境中每种细胞类型的空间分布。我们的分析为了解人类肝脏恶性肿瘤提供了资源，并可能揭示潜在的干预点。