A single cell atlas of the human liver tumor microenvironment

We identify the specific contribution of each cell type to the human liver tumor microenvironment and reconstructed hepatocytes zonation of the human liver using a combined approach of single-cell RNA sequencing and laser capture microdissection. Our work constitutes an important resource for identifying potential sources of vulnerabilities in liver tumors and metastases. We analyzed six patients who underwent liver resection (colorectal metastasis, primary cholangiocarcinoma, and benign liver cyst). Two samples were extracted from each (malignant and non-malignant). All samples underwent single cells RNA sequencing using MARSseq. In parallel, frozen sections were prepared from each sample. Isolated specific zones of each sections was extracted using laser capture microdissection (LCM) and subjected to bulk sequencing using mcSCRBseq protocol.

本研究通过单细胞RNA测序（single-cell RNA sequencing）与激光捕获显微切割（laser capture microdissection, LCM）联合技术，明确了各类细胞对人类肝脏肿瘤微环境的具体贡献，并重构了人类肝脏的肝细胞分区结构。本研究成果可为识别肝脏肿瘤及转移瘤的潜在致病脆弱靶点提供重要的参考资源。本研究纳入6例行肝脏切除术的患者，其病灶类型涵盖结直肠肝转移瘤、原发性胆管细胞癌及肝脏良性囊肿。每位患者分别采集恶性与非恶性组织样本各1份。所有样本均采用MARSseq技术完成单细胞RNA测序。与此同时，为每份样本制备冰冻切片，通过激光捕获显微切割技术分离提取每张切片的特定区域，并采用mcSCRBseq实验流程进行批量测序。