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Series GSE137787 Query DataSets for GSE137787
Status Public on Sep 27, 2019
Title Bulk transcriptomic analysis of two models of zebrafish beta-catenin-driven HCC
Organism Danio rerio
Experiment type Expression profiling by high throughput sequencing
Summary Up to 41% of hepatocellular carcinomas (HCCs) result from activating mutations in the CTNNB1 gene encoding β-catenin. β-catenin has dual cellular functions as a component of the Wnt signaling pathway and adherens junctions. HCC-associated CTNNB1 mutations stabilize the β-catenin protein, leading to nuclear and/or cytoplasmic localization of β-catenin and downstream activation of Wnt target genes. In patient HCC samples, β-catenin nuclear and cytoplasmic localization are typically patchy, even among HCC with highly active CTNNB1 mutations. The functional and clinical relevance of this heterogeneity in β-catenin activation are not well understood. To define mechanisms of β-catenin-driven HCC initiation, we generated a Cre-lox system that enabled switching on activated β-catenin in 1) a small number of hepatocytes in early development; or 2) the majority of hepatocytes in later development or adulthood. We discovered that switching on activated β-catenin in a subset of larval hepatocytes was sufficient to drive HCC initiation. To determine the role of Wnt/β-catenin signaling heterogeneity later in hepatocarcinogenesis, we performed RNA-seq analysis of zebrafish β-catenin-driven HCC. Ingenuity Pathway Analysis of differentially expressed genes in the Cre-lox HCC model revealed that “Cancer” and “Liver Tumor” categories were significantly altered, indicating transcriptional similarities with human HCC and other vertebrate HCC models. At the single-cell level, 2.9% to 15.2% of hepatocytes from zebrafish β-catenin-driven HCC expressed two or more of the Wnt target genes axin2, mtor, glula, myca, and wif1, indicating focal activation of Wnt signaling in established tumors. Thus, heterogeneous β-catenin activation drives HCC initiation and persists throughout hepatocarcinogenesis.
 
Overall design Examination of HCC and nonHCC liver samples from two different models of zebrafish, compared to wildtype/nonHCC siblings.
 
Contributor(s) Kalasekar SM, Kotiyal S, Conley C, Phan C, Young A, Evason KJ
Citation(s) 31575545
Submission date Sep 20, 2019
Last update date Nov 12, 2019
Contact name Kimberley Jane Evason
Organization name University of California, San Francisco
Department Pathology
Street address 513 Parnassus Ave, Room M545
City San Francisco
State/province CA
ZIP/Postal code 94143
Country USA
 
Platforms (1)
GPL24995 Illumina NovaSeq 6000 (Danio rerio)
Samples (20)
GSM4087861 604
GSM4087862 605
GSM4087863 630
This SubSeries is part of SuperSeries:
GSE137788 Transcriptomic analysis of two models of zebrafish beta-catenin-driven HCC
Relations
BioProject PRJNA573071
SRA SRP222804

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE137787_15743R_counts.txt.gz 431.6 Kb (ftp)(http) TXT
GSE137787_16048R_counts.txt.gz 415.5 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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