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Hepatology. 2018 Jul;68(1):127-140. doi: 10.1002/hep.29778. Epub 2018 May 9.

Single-cell analysis reveals cancer stem cell heterogeneity in hepatocellular carcinoma.

Author information

1
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
2
Translational Research Unit, Chulabhorn Research Institute, Bangkok, Thailand.
3
Flow Cytometry Core Facility, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
4
Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
5
Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD.

Abstract

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. (Hepatology 2018;68:127-140).

PMID:
29315726
PMCID:
PMC6033650
[Available on 2019-07-01]
DOI:
10.1002/hep.29778

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