Divergent WNT Signaling and Drug Sensitivity Profiles within Hepatoblastoma Tumors and Organoids

Hepatoblastoma, the most prevalent pediatric liver cancer, almost always carries a WNT-activating CTNNB1 mutation, yet exhibits notable molecular heterogeneity. To characterize this heterogeneity and identify novel targeted therapies, we perform comprehensive analysis of hepatoblastomas and tumor-derived organoids using single-cell RNA-seq/ATAC-seq, spatial transcriptomics, and high-throughput drug profiling. We identify two distinct tumor epithelial signatures: hepatic ‘fetal’ and WNT-high ‘embryonal’, displaying divergent WNT signaling patterns. The fetal group is enriched for liver-specific WNT targets, while the embryonal group is enriched in canonical WNT target genes.

Type: Transcriptome Sequencing
Archiver: European Genome-Phenome Archive (EGA)

4 Datasets 1 Publication

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD50000000794	10X Genomics single-cell transcriptomics of hepatoblastoma tissues using Chromium Next GEM Single-Cell 3’ Reagent Kits v3.1. Single-cell transcriptomics data (bam files) of PT9, post-chemotherapy tumor sample, and PT13, treatment naive tumor sample. Single-cell solutions were obtained from viably frozen tissue samples using enzymatic digestion.	Illumina NovaSeq 6000	2
EGAD50000000795	10X Genomics single-cell multiome profiling of hepatoblastoma tumor organoids using Chromium Next GEM Single-Cell Multiome ATAC + Gene Expression Kit. Single-cell transcriptomics data (bam file) of multiplexed sample of hepatoblastoma tumor organoids: 3E, 8F1, 10F2, 13F2, 13E, 17E and 96F1. Single-cell solutions were obtained from fresh organoid samples using enzymatic digestion.	Illumina NovaSeq 6000	7
EGAD50000000796	10X Genomics single-cell transcriptomic profiling of hepatoblastoma tumor organoids using Chromium Next GEM Single-Cell 3’ Reagent Kits v3.1 or 3’ CellPlex Multiplexing Kit. Single-cell transcriptomics data (bam files) of hepatoblastoma tumor organoids: 3E, 8F1, 10F2, 13F2, 13F2 late, 13E, 17E, 17F1, 22E, 27F1, 28F1, 31E, 96F1, 121E and 135. Single-cell solutions were obtained from fresh organoid samples using enzymatic digestion.	Illumina NovaSeq 6000	15
EGAD50000000797	10X Genomics Visium Spatial transcriptomics analysis of hepatoblastoma and adjacent normal liver. Spatial data of normal liver and PT2 (fastq files), and and PT13, PT14 and PT16 (bam files) using the Visium Spatial Gene Expression Solution. All samples, except PT13, were collected post-chemotherapy.	Illumina NovaSeq 6000	5

Publications	Citations
Divergent WNT signaling and drug sensitivity profiles within hepatoblastoma tumors and organoids. Kluiver TA, Lu Y, Schubert SA, Kraaier LJ, Ringnalda F, Lijnzaad P, DeMartino J, Megchelenbrink WL, Amo-Addae V, Eising S, de Faria FW, Münter D, van de Wetering M, Kerl K, Duiker E, van den Heuvel MC, de Meijer VE, de Kleine RH, Molenaar JJ, Margaritis T, Stunnenberg HG, de Krijger RR, Zsiros J, Clevers H, Peng WC. Nat Commun 15: 2024 8576	1

Publications

Citations

Divergent WNT signaling and drug sensitivity profiles within hepatoblastoma tumors and organoids.
Kluiver TA, Lu Y, Schubert SA, Kraaier LJ, Ringnalda F, Lijnzaad P, DeMartino J, Megchelenbrink WL, Amo-Addae V, Eising S, de Faria FW, Münter D, van de Wetering M, Kerl K, Duiker E, van den Heuvel MC, de Meijer VE, de Kleine RH, Molenaar JJ, Margaritis T, Stunnenberg HG, de Krijger RR, Zsiros J, Clevers H, Peng WC. Nat Commun 15: 2024 8576