Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Cancer letters, 2019-09, Vol.459, p.176-185

Ort / Verlag

Ireland: Elsevier B.V

Erscheinungsjahr

2019

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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. •Single-cell transcriptomics dissected the intra-tumoral heterogeneity of hepatocellular carcinoma (HCC).•HCC single cells showed two distinct major cell populations according to EPCAM expression.•CD24+/CD44+-enriched cell subpopulation was identified within the EPCAM+ cells.•CTSE was the most upregulated signature gene in CD24+/CD44+-enriched cells.•Knockdown of CTSE significantly reduced self-renewal ability in vitro and tumorigenicity in vivo.