GPNMB+Gal‐3+ hepatic parenchymal cells promote immunosuppression and hepatocellular carcinogenesis

• DOI: 10.15252/embj.2023114060
• Publication Date: 2023-11-27T22:51:40Z
• Authors: Yan Meng; Qiudong Zhao; Yan Sang; Jianping Liao; Fei Ye; Shuping Qu; Pingping Nie; Liwei An; Weihong Zhang; Shi Jiao; Aimin Huang; Zhaocai Zhou; Lixin Wei
• Keywords: Parenchyma; Immunosuppression; Malignant Transformation

Abstract Hepatocellular carcinoma (HCC) formation is a multi‐step pathological process that involves evolution of heterogeneous immunosuppressive tumor microenvironment. However, the specific cell populations involved and their origins contribution to HCC development remain largely unknown. Here, comprehensive single‐cell transcriptome sequencing was applied profile rat models toxin‐induced liver tumorigenesis patients. Specifically, we identified three hepatic parenchymal cells emerging during progression, termed metabolic hepatocytes (HC Meta ), Epcam + population with differentiation potential (EP +Diff ) malignant transformation subset (MT Immu ). These distinct subpopulations form an oncogenic trajectory depicting dynamic landscape hepatocarcinogenesis, signature genes reflecting transition from EP MT . Importantly, GPNMB Gal‐3 exhibit both properties. Moreover, SOX18 required for generation cells. Enrichment found be associated poor prognosis higher rate recurrence in Collectively, unraveled progression atlas uncovered as major contributing microenvironment thus malignance HCC.