Hepatocellular carcinoma (HCC) is an aggressive disease with a poor clinical outcome. The cancer stem cell (CSC) model states that tumour growth is powered by a subset of tumour stem cells within cancers. This model explains several clinical observations in HCC (as well as in other cancers), including the almost inevitable recurrence of tumours after initial successful chemotherapy and/or radiotherapy, as well as the phenomena of tumour dormancy and treatment resistance. The past two decades have seen a marked increase in research on the identification and characterization of liver CSCs, which has encouraged the design of novel diagnostic and treatment strategies for HCC. These studies revealed novel aspects of liver CSCs, including their heterogeneity and unique immunobiology, which are suggestive of opportunities for new research directions and potential therapies. In this Review, we summarize the present knowledge of liver CSC markers and the regulators of stemness in HCC. We also comprehensively describe developments in the liver CSC field with emphasis on experiments utilizing single-cell transcriptomics to understand liver CSC heterogeneity, lineage-tracing and cell-ablation studies of liver CSCs, and the influence of the CSC niche and tumour microenvironment on liver cancer stemness, including interactions between CSCs and the immune system. We also discuss the potential application of liver CSC-based therapies for treatment of HCC.

肝细胞癌 (HCC) 是一种侵袭性疾病，临床结果不佳。癌症干细胞 (CSC) 模型指出，肿瘤生长是由癌症中的一部分肿瘤干细胞驱动的。该模型解释了 HCC（以及其他癌症）中的一些临床观察结果，包括在最初成功的化疗和/或放疗后几乎不可避免的肿瘤复发，以及肿瘤休眠和治疗耐药现象。在过去的二十年里，对肝脏 CSC 的鉴定和表征的研究显着增加，这鼓励了针对 HCC 的新型诊断和治疗策略的设计。这些研究揭示了肝脏 CSC 的新方面，包括它们的异质性和独特的免疫生物学，这暗示了新研究方向和潜在疗法的机会。在这篇综述中，我们总结了目前关于肝脏 CSC 标志物和 HCC 干细胞调节因子的知识。我们还全面描述了肝脏 CSC 领域的发展，重点是利用单细胞转录组学了解肝脏 CSC 异质性的实验、肝脏 CSC 的谱系追踪和细胞消融研究，以及 CSC 生态位和肿瘤微环境对肝癌的影响干性，包括 CSC 和免疫系统之间的相互作用。我们还讨论了基于肝 CSC 的疗法在 HCC 治疗中的潜在应用。我们还全面描述了肝脏 CSC 领域的发展，重点是利用单细胞转录组学了解肝脏 CSC 异质性的实验、肝脏 CSC 的谱系追踪和细胞消融研究，以及 CSC 生态位和肿瘤微环境对肝癌的影响干性，包括 CSC 和免疫系统之间的相互作用。我们还讨论了基于肝 CSC 的疗法在 HCC 治疗中的潜在应用。我们还全面描述了肝脏 CSC 领域的发展，重点是利用单细胞转录组学了解肝脏 CSC 异质性的实验、肝脏 CSC 的谱系追踪和细胞消融研究，以及 CSC 生态位和肿瘤微环境对肝癌的影响干性，包括 CSC 与免疫系统之间的相互作用。我们还讨论了基于肝 CSC 的疗法在 HCC 治疗中的潜在应用。