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Single‐cell analysis reveals cancer stem cell heterogeneity in hepatocellular carcinoma
Author(s) -
Zheng Hongping,
Pomyen Yotsawat,
Hernandez Maria Olga,
Li Caiyi,
Livak Ferenc,
Tang Wei,
Dang Hien,
Greten Tim F.,
Davis Jeremy L.,
Zhao Yongmei,
Mehta Monika,
Levin Yelena,
Shetty Jyoti,
Tran Bao,
Budhu Anuradha,
Wang Xin Wei
Publication year - 2018
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.29778
Subject(s) - hepatocellular carcinoma , cancer stem cell , transcriptome , biology , cancer research , genetic heterogeneity , cell , stem cell , single cell analysis , cancer , gene , phenotype , genetics , gene expression
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. Conclusion: 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. (H epatology 2018;68:127‐140).