Single-cell transcriptomics uncovers cellular architecture and developmental trajectories in hepatoblastoma

Area of Science:

• Pediatric oncology
• Cancer genomics
• Single-cell biology

Background:

• Hepatoblastoma (HB) is the primary liver cancer in children.
• Limited treatment options exist for advanced HB.
• Understanding HB's cellular and molecular basis is crucial for improved therapies.

Purpose of the Study:

• To dissect the cellular and molecular drivers of hepatoblastoma (HB) oncogenesis and heterogeneity.
• To establish a single-cell transcriptomic landscape of HB.
• To identify potential therapeutic targets for advanced HB.

Main Methods:

• Single-cell transcriptome profiling of tumor and adjacent liver tissues from five HB patients.
• Deconvolution analysis integrating single-cell and bulk transcriptomes.
• Comparative analysis with early human liver development transcriptomes.

Main Results:

• Seven distinct tumor cell subpopulations in HB were identified.
• A novel HB subtyping method based on cell composition was developed.
• HB tumor cell hierarchy mirrors early liver development and aligns with cancer stem cell models.
• FACT inhibition emerged as a potential therapeutic strategy against a specific HB subpopulation and subtype.

Conclusions:

• Integrative analyses revealed the cellular architecture and developmental trajectories of HB.
• A framework for developing targeted diagnostics and therapeutics for HB was established.
• Single-cell analysis provides critical insights into HB biology and treatment strategies.