Single cell transcriptomics unveiled that early life BDE-99 exposure reprogrammed the gut-liver axis to promote a pro-inflammatory metabolic signature in male mice at late adulthood (Part 2/2)

Polybrominated diphenyl ethers (PBDEs) are legacy flame retardants that bioaccumulate in the environment.  The gut microbiome is an important regulator of liver functions including xenobiotic biotransformation and immune regulation.  We recently showed that neonatal exposure to BDE-99, a human breast milk-enriched PBDE congener, up-regulated pro-inflammation- and down-regulated drug metabolism-related genes predominantly in males in young adulthood.  However, it remains unknown regarding the persistence of dysregulation into late adulthood, differential impact of hepatic cell types, and the involvement of the gut microbiome from neonatal BDE-99 exposure.  To address these knowledge gaps, male C57BL/6 mouse pups were orally exposed to corn oil (10 ml/kg) or BDE-99 (57 mg/kg) once daily from postnatal days 2-4.  At 15 months of age, neonatal BDE-99 exposure down-regulated key xenobiotic- and lipid metabolizing enzymes and up-regulated genes involved in microbial influx in hepatocytes.  Ne..., Chemicals and dosing regimen
2,2’,4,4’,5-pentabromodiphenyl ether (BDE-99 [CAS No. 60348-60-9]) was purchased from AccuStandard, Inc. (New Haven, Connecticut).  Corn oil was purchased from Sigma-Aldrich (St. Louis, MO).  BDE-99 was dissolved in corn oil and filtered using a 0.22 μm Millipore Express Plus Membrane filter (EMD Millipore, Temecula, California).  All mice used in this study were housed according to the Association for Assessment and Accreditation of Laboratory Animal Care International guidelines.  The study was approved by the University of Washington Institutional Animal Care and Use Committee.  Eight-week-old specific pathogen-free C57BL/6J mice were purchased from the Jackson Laboratory (Bay Harbor, Maine), and were acclimated to the animal housing facility at the University of Washington for at least three breeding generations.  Mice were housed in standard air-filtered cages using autoclaved bedding (autoclaved Enrich-N’Pure, Andersons, Maumee, OH).  Mice had ad libit..., , # Single cell transcriptomics unveiled that early life BDE-99 exposure reprogrammed the gut-liver axis to promote a pro-inflammatory metabolic signature in male mice at late adulthood (Part 2/2)

Description of the data and file structure

The repository contains part 1 of 2 data of mouse single cell RNA sequencing fastq files which can be processed using the cell ranger pipeline (10X Genomics). 

Part 1 contains 6 samples comparing the cell type-specific gene expression profiles using adult mouse livers neonatally exposed to BDE-99: DOI: 10.5061/dryad.4mw6m90gm 

Part 2 (this dataset) contains 6 samples to investigate the necessity of the microbiome in regulating the hepatic transcriptome in mice: DOI: 10.5061/dryad.8931zcrzx 

The Dryad file upload contains the raw single cell RNA sequencing (scRNA-seq) data comparing conventional (i.e., with microbiome) and germ-free (i.e., without microbiome) wild type (C57BL/6) mice. Mice were 7-8 month old and scRNA-seq was performed using dissoc...