Single-cell analysis reveals cancer stem cell heterogeneity in hepatocellular carcinoma.
Zheng H1, Pomyen Y1,2, Hernandez MO1, Li C3, Livak F3, Tang W1, Dang H1, Greten TF4, Davis JL4, Zhao Y5, Mehta M5, Levin Y5, Shetty J5, Tran B5, Budhu A1, Wang XW1.
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).