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| Status |
Public on Aug 28, 2017 |
| Title |
Novel Interactions between Gut Microbiome and Host Drug-processing Genes Modify the Hepatic Metabolism of the Environmental Chemicals PBDEs |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Purpose: Next-generation sequencing (NGS) has been utilized for systems-based analysis of all liver samples. The goals of this study were to compare the hepatic transcriptome and PBDE metabolism between conventional (CV) and germ-free (GF) mice.
Methods: Livers from vehicle (corn oil), BDE-47, or BDE-99 treated adult male CV and GF mice were used for RNA-Seq (biological replicates: n=3 for CV corn oil, n=4 for CV BDE-47, n=2 for CV BDE-99, n=3 for GF corn oil, n=3 for GF BDE-47, and n=3 for BDE-99) using a HiSeq 2000 sequencer. The sequence reads that passed quality filters were mapped to the mouse reference genome (mm10) using HISAT v 0.1.6 beta; transcript abundance and differential expression were determined using Cufflinks (CuffDiff) v 2.2.1.
Results: Using an optimized data analysis workflow,RNA-Seq generated approximately 47 to 68 million reads per sample, among which approximately 40 to 60 million reads were uniquely mapped to the mouse reference genome (NCBI GRCm/38/mm10). And we identified 393 drug processing genes in the livers of WT and hCAR-TG with with HISAT workflow. RNA-seq data confirmed that among all the 393 DPGs with known important functions in xenobiotic biotransformation, 90 DPGs were not expressed in livers of any groups (threshold: average FPKM < 1 in all treatment groups); whereas a total of 303 genes were expressed in livers of at least one groups, among which 258 DPGs were differentially regulated by mCAR or hCAR activation in either Day 5 or Day 60 (FDR-BH<0.05), and 45 genes were stably expressed among all treatment groups.
Conclusions: Our study has unveiled a novel interaction between gut microbiome and the hepatic biotransformation of PBDEs, demonstrating that germ-free conditions modified the hepatic oxidation of PBDEs as well as the expression of relevant drug-processing genes in liver.
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| Overall design |
CV and GF male mice at the age of 9-weeks were treated with corn oil, BDE-47 (100umol/kg), or BDE-99 (100umol/kg) once daily for 4 consecutive days, and tissues were collected 24h after the final dose. Total RNAs were isolated from livesr using RNA zol bee reagent, and were subjected to RNA-Seq using a HiSeq 2000 sequencer.
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| Contributor(s) |
Cui JY, Li CY, Cade S, Kuo L, Schultz IR, Bhatt DK, Prasad B, Bammler TK, Lee S |
| Citation(s) |
28864748, 30067809 |
| Submission date |
Jul 19, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
James William MacDonald |
| E-mail(s) |
jmacdon@uw.edu
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| Organization name |
University of Washington
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| Department |
Environmental and Occupational Health Sciences
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| Street address |
4225 Roosevelt Way NE
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| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98105-6099 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA395063 |
| SRA |
SRP112908 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE101650_RAW.tar |
13.8 Mb |
(http)(custom) |
TAR (of FPKM_TRACKING) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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