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

TitleSingle-cell transcriptomics reveals the landscape of intra-tumoral heterogeneity and stemness-related subpopulations in liver cancer
Authors
KeywordsSingle-cell sequencing
Tumor heterogeneity
HCC
Cancer stem cell
Cancer stemness
Issue Date2019
PublisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/canlet
Citation
Cancer Letters, 2019, v. 459, p. 176-185 How to Cite?
AbstractHepatocellular 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.
Persistent Identifierhttp://hdl.handle.net/10722/272350
ISSN
2019 Impact Factor: 7.36
2015 SCImago Journal Rankings: 2.331

 

DC FieldValueLanguage
dc.contributor.authorHo, DWH-
dc.contributor.authorTsui, YM-
dc.contributor.authorSze, KMF-
dc.contributor.authorChan, LK-
dc.contributor.authorCheung, TT-
dc.contributor.authorLee, E-
dc.contributor.authorSham, PC-
dc.contributor.authorTsui, SKW-
dc.contributor.authorLee, TKW-
dc.contributor.authorNg, IOL-
dc.date.accessioned2019-07-20T10:40:36Z-
dc.date.available2019-07-20T10:40:36Z-
dc.date.issued2019-
dc.identifier.citationCancer Letters, 2019, v. 459, p. 176-185-
dc.identifier.issn0304-3835-
dc.identifier.urihttp://hdl.handle.net/10722/272350-
dc.description.abstractHepatocellular 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.-
dc.languageeng-
dc.publisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/canlet-
dc.relation.ispartofCancer Letters-
dc.subjectSingle-cell sequencing-
dc.subjectTumor heterogeneity-
dc.subjectHCC-
dc.subjectCancer stem cell-
dc.subjectCancer stemness-
dc.titleSingle-cell transcriptomics reveals the landscape of intra-tumoral heterogeneity and stemness-related subpopulations in liver cancer-
dc.typeArticle-
dc.identifier.emailHo, DWH: dwhho@hku.hk-
dc.identifier.emailTsui, YM: ymtsui@hku.hk-
dc.identifier.emailSze, KMF: karensze@hkucc.hku.hk-
dc.identifier.emailChan, LK: lkchan1@hku.hk-
dc.identifier.emailCheung, TT: cheung68@hku.hk-
dc.identifier.emailLee, E: qihua@hkucc.hku.hk-
dc.identifier.emailSham, PC: pcsham@hku.hk-
dc.identifier.emailNg, IOL: iolng@hku.hk-
dc.identifier.authorityHo, DWH=rp02285-
dc.identifier.authorityChan, LK=rp02289-
dc.identifier.authorityCheung, TT=rp02129-
dc.identifier.authoritySham, PC=rp00459-
dc.identifier.authorityNg, IOL=rp00335-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.canlet.2019.06.002-
dc.identifier.pmid31195060-
dc.identifier.scopuseid_2-s2.0-85067204652-
dc.identifier.hkuros298778-
dc.identifier.volume459-
dc.identifier.spage176-
dc.identifier.epage185-
dc.publisher.placeIreland-

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