ADMSC01 mRNA-Seq paired end data
ADMSC03 mRNA-Seq paired end data
scRNA-seq analysis of 384 placental immune cells
ChIPseq targeting the cohesin subunit STAG1 in STAG2-mutated AMLs or cohesin wildtype AMLs
A IPS01_N_Fibroblast_smRNA-Seq single end data for iPSC(Oct4)
A IPS04_X_Fibroblast_mRNA-Seq paired end data for iPSC(Oct4)
A IPS01_N_Fibroblast_mRNA-Seq paired end data for iPSC(Oct4)
McGill EMC Release 4 for assay "ChIP-Seq Input"
A IPS04_X_Fibroblast_smRNA-Seq single end data for iPSC(Oct4)
Hepatoblastoma (HB) is the most common pediatric liver tumor, affecting mostly children under 3 years of age. This rare tumor represents 1% of all pediatric cancers. Genetic studies have shown that HB is characterized by high frequency mutations of the CTNNB1 gene encoding beta-catenin (around 75%) and relative genomic stability. Here we have analyzed the transcriptional profile of 21 HBs compared to matched non-tumor livers by Cap Analysis of Gene Expression (CAGE), which provides accurate and quantitative profiling of all transcripts. CAGE analysis revealed strong upregulation of known Wnt target coding genes in most tumors analyzed, consistent with previous transcriptomic studies. To better define the Wnt-dependent transcriptional landscape of HB, we integrated CAGE data with TCF4 ChIP-seq data from a CTNNB1-mutated cancer cell line and with the FANTOM5 genomic coordinates of TCF/LEF binding motifs. Both TCF/LEF binding motifs and ChIP-seq peaks were strongly enriched in the immediate upstream region, not only for protein-coding genes, but also for non-coding transcripts. Among the selected 112 top Wnt target genes at FDR<1.0E-6 and fold change>8, we found clear over-representation (66%) of distant transcription start sites (TSSs) representing lncRNAs and enhancer RNAs, which raises the question of their role in HB pathogenesis. Analysis of the 112 promoters using CAGEd-oPOSSUM confirmed the predominant involvement of Tcf/Lef transcription factors, together with HNF4G, GATA2, Sox3 and Ets-related genes. Finally, the 112 Wnt target signature defined 3 tumor subclasses, T1, T2 and T3, characterized by progressive alteration of the non-coding part of the transcriptome and significant differences in clinical behavior.
