Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Translational Research Unit, Chulabhorn Research Institute, Bangkok, Thailand.
Hepatology. 2018 Jul;68(1):127-140. doi: 10.1002/hep.29778. Epub 2018 May 9.
Intratumor molecular heterogeneity of hepatocellular carcinoma is partly attributed to the presence of hepatic cancer stem cells (CSCs). Different CSC populations defined by various cell surface markers may contain different oncogenic drivers, posing a challenge in defining molecularly targeted therapeutics. We combined transcriptomic and functional analyses of hepatocellular carcinoma cells at the single-cell level to assess the degree of CSC heterogeneity. We provide evidence that hepatic CSCs at the single-cell level are phenotypically, functionally, and transcriptomically heterogeneous. We found that different CSC subpopulations contain distinct molecular signatures. Interestingly, distinct genes within different CSC subpopulations are independently associated with hepatocellular carcinoma prognosis, suggesting that a diverse hepatic CSC transcriptome affects intratumor heterogeneity and tumor progression.
Our work provides unique perspectives into the biodiversity of CSC subpopulations, whose molecular heterogeneity further highlights their role in tumor heterogeneity, prognosis, and hepatic CSC therapy. (Hepatology 2018;68:127-140).
肝癌肿瘤内分子异质性部分归因于肝癌干细胞（CSC）的存在。不同的 CSC 群体由各种细胞表面标志物定义，可能包含不同的致癌驱动因素，这给确定分子靶向治疗带来了挑战。我们结合了单细胞水平的肝癌细胞的转录组和功能分析，以评估 CSC 异质性的程度。我们提供的证据表明，单细胞水平的肝 CSCs 在表型、功能和转录组上是异质的。我们发现不同的 CSC 亚群具有不同的分子特征。有趣的是，不同 CSC 亚群中的不同基因与肝癌的预后独立相关，这表明不同的肝 CSC 转录组会影响肿瘤内异质性和肿瘤进展。
我们的工作为 CSC 亚群的多样性提供了独特的视角，其分子异质性进一步强调了它们在肿瘤异质性、预后和肝 CSC 治疗中的作用。（《肝脏病学》2018；68：127-140）。
