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  1. Home
  2. Research Domains
  3. Biomedical And Clinical Sciences
  4. Oncology And Carcinogenesis
  5. Predictive And Prognostic Markers
  6. Lineage Tracing And Single-cell Analysis Reveal Proliferative Prom1+ Tumour-propagating Cells And Their Dynamic Cellular Transition During Liver Cancer Progression.

Lineage tracing and single-cell analysis reveal proliferative Prom1+ tumour-propagating cells and their dynamic cellular transition during liver cancer progression.

Lei Zhou1,2, Ken Ho Yu1,3, Tin Lok Wong1,4

  • 1School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

Gut
|September 30, 2021

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Generation of Subcutaneous and Intrahepatic Human Hepatocellular Carcinoma Xenografts in Immunodeficient Mice
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View abstract on PubMed

Summary
This summary is machine-generated.

Prominin-1 (Prom1) marks liver cancer stem cells (CSCs) in hepatocellular carcinoma (HCC). These Prom1+ cells drive tumor growth and heterogeneity, and their depletion hinders cancer progression, offering new therapeutic targets.

Area of Science:

  • Oncology
  • Stem Cell Biology
  • Genomics

Background:

  • Hepatocellular carcinoma (HCC) exhibits significant intratumoral heterogeneity, leading to therapeutic resistance and recurrence.
  • Prominin-1 (PROM1)/CD133 is identified as a key marker for liver cancer stem cells (CSCs) in human HCC.

Purpose of the Study:

  • To investigate the heterogeneity and properties of Prominin-1 positive (Prom1+) cells within HCC using intact mouse models.
  • To elucidate the role of Prom1+ cells in HCC progression and therapeutic resistance.

Main Methods:

  • Establishment of two distinct mouse models for chronic fibrotic and rapid steatosis-related HCC.
  • In vivo lineage tracing and targeted cell depletion using genetically modified mouse lines (Prom1C-L/+; Rosa26tdTomato/+ and Prom1C-L/+; Rosa26DTA/+).
Keywords:
hepatocellular carcinomastem cells

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  • Single-cell RNA sequencing (scRNA-seq) to analyze the transcriptomic profile of Prom1+ cells.
  • Main Results:

    • Prom1+ cells in HCC tumors function as proliferative, tumor-propagating cells with CSC-like properties and undergo clonal expansion in situ.
    • These cells demonstrate increased tumorigenicity in 3D culture and allotransplantation, with the potential to form diverse cancer lineages.
    • Depletion of Prom1+ cells significantly impedes tumor growth and reduces malignant characteristics in both HCC models.
    • scRNA-seq revealed heterogeneity within Prom1+ HCC cells, showing a trajectory towards dedifferentiation with high proliferation and stem cell traits.
    • A conserved gene signature in Prom1 lineage cells predicts poor prognosis in human HCC.
    • Activated oxidant detoxification pathways were identified as a mechanism supporting dedifferentiation and lineage propagation.

    Conclusions:

    • The study reveals the heterogeneity and dynamic behavior of Prom1+ HCC cells using in vivo lineage tracing and scRNA-seq.
    • Prom1+ cells are crucial drivers of HCC progression, exhibiting CSC-like properties and contributing to tumor heterogeneity.
    • Targeting Prom1+ cells presents a promising therapeutic strategy for overcoming resistance and recurrence in HCC.