Single-cell transcriptomics reveals the landscape of intra-tumoral heterogeneity and stemness-related subpopulations in liver cancer

Daniel Wai Hung Ho, Yu Man Tsui, Karen Man Fong Sze, Lo Kong Chan, Tan To Cheung, Eva Lee, Pak Chung Sham, Stephen Kwok Wing Tsui, Terence Kin Wah Lee, Irene Oi Lin Ng

Research output: Journal article publicationJournal articleAcademic researchpeer-review

26 Citations (Scopus)

Abstract

Hepatocellular carcinoma (HCC) is heterogeneous, rendering its current curative treatments ineffective. The emergence of single-cell genomics represents a powerful strategy in delineating the complex molecular landscapes of cancers. In this study, we demonstrated the feasibility and merit of using single-cell RNA sequencing to dissect the intra-tumoral heterogeneity and analyze the single-cell transcriptomic landscape to detect rare cell subpopulations of significance. Exploration of the inter-relationship among liver cancer stem cell markers showed two distinct major cell populations according to EPCAM expression, and the EPCAM+ cells had upregulated expression of multiple oncogenes. We also identified a CD24+/CD44+-enriched cell subpopulation within the EPCAM+ cells which had specific signature genes and might indicate a novel stemness-related cell subclone in HCC. Notably, knockdown of signature gene CTSE for CD24+/CD44+ cells significantly reduced self-renewal ability on HCC cells in vitro and the stemness-related role of CTSE was further confirmed by in vivo tumorigenicity assays in nude mice. In summary, single-cell genomics is a useful tool to delineate HCC intratumoral heterogeneity at better resolution. It can identify rare but important cell subpopulations, and may guide better precision medicine in the long run.

Original languageEnglish
Pages (from-to)176-185
Number of pages10
JournalCancer Letters
Volume459
DOIs
Publication statusPublished - 10 Sep 2019

Keywords

  • Cancer stem cell
  • Cancer stemness
  • HCC
  • Single-cell sequencing
  • Tumor heterogeneity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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