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Updated: May 11, 2026
10:06
Cell Type-specific Gene Expression Profiling in the Mouse Liver
Published on: September 17, 2019
RNA-Seq profiling reveals novel hepatic gene expression pattern in aflatoxin B1 treated rats
B Alex Merrick1, Dhiral P Phadke, Scott S Auerbach
1Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America. merrick@niehs.nih.gov
Plos One
|May 1, 2013
Summary
Deep sequencing revealed thousands of gene expression changes in rat livers exposed to aflatoxin B1 (AFB1) before visible damage occurred. This method identified novel transcripts and pathways involved in AFB1-induced liver cancer.
Area of Science:
- Toxicogenomics
- Molecular Biology
- Cancer Research
Background:
- Aflatoxin B1 (AFB1) is a potent hepatocarcinogen.
- Early molecular changes in AFB1-induced liver carcinogenesis are not fully understood.
- Histopathological lesions and tumors appear late in AFB1 exposure.
Purpose of the Study:
- To investigate the subchronic effects of AFB1 on the male rat liver transcriptome using deep sequencing.
- To compare RNA-Seq with microarray analysis for detecting differentially expressed genes (DEGs).
- To identify novel transcripts and pathways involved in AFB1 carcinogenesis.
Main Methods:
- Subchronic exposure of male rats to 1 ppm AFB1 or feed controls (CTRL).
- RNA-Sequencing (RNA-Seq) for transcriptome analysis.
- Bioinformatic analysis using TopHat, DESeq, and Cufflinks-Cuffdiff.
- Quantitative PCR (qPCR) for validation.
Main Results:
- RNA-Seq identified 1,026 differentially expressed transcripts (DEGs) with >2-fold change (p<0.005), significantly more than microarray (626 transcripts).
- Pathway analysis revealed AFB1-responsive networks including Ahr, Nrf2, xenobiotic metabolism, cell cycle, and E2f1-related pathways.
- 49 novel, differentially-expressed transcripts were identified, including two unannotated hepatic AFB1-responsive transcripts (HAfTs).
Conclusions:
- RNA-Seq provides greater sensitivity and resolution than microarrays for detecting AFB1-induced transcriptomic changes.
- The study identified novel AFB1-responsive transcripts and exons, offering new insights into early carcinogenesis mechanisms.
- Findings support RNA-Seq's utility in uncovering previously unidentified molecular events in AFB1-mediated liver cancer development.
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01:58Cell Specific Gene Expression
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