Intratumor molecular heterogeneity of hepatocellular carcinoma (HCC) 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 molecular-targeted therapeutics. We combined transcriptomic and functional analyses of HCC 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 transcriptionally heterogeneous. We found that different CSC subpopulations contain distinct molecular signatures. Interestingly, distinct genes within different CSC subpopulations are independently associated with HCC prognosis, suggesting that a diverse hepatic CSC transcriptome affects intratumor heterogeneity and tumor progression.
Our work provides unique perspectives into the previously unappreciated diversity of CSC subpopulations, whose molecular heterogeneity further highlights their role in tumor heterogeneity, prognosis and hepatic CSC therapy. This article is protected by copyright. All rights reserved.
© 2018 by the American Association for the Study of Liver Diseases.