Superfund Research Program
Title: Application of singe nuclei RNA sequencing to assess the hepatic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin
Accession Number: GSE148339
Link to Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE148339
Repository: Gene Expression Omnibus (GEO)
Data Type(s): Gene Expression
Experiment Type(s): Expression profiling by high throughput sequencing
Organism(s): Mus musculus
Summary: Cell-specific transcriptional responses are lost in the averages of bulk RNA sequencing. We performed single nuclei RNA sequencing (snSeq) on frozen liver samples from male C57BL/6 mice in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Approximately 19,907 hepatic genes were detected across 16,015 sequenced nuclei from control and treated samples. Eleven cell-(sub)types were identified including distinct hepatocyte sub-populations, consistent with the cell diversity of the liver. TCDD increased macrophages from 0.5 to 24.7 , while neutrophils were only present in treated samples. The number of differentially expressed genes correlated with the basal expression level of Ahr. In addition to expected functional enrichments within each cell-(sub)type, RAS signaling was enriched in nonparenchymal cells. snSeq also identified a Kupffer cell subtype highly expressing Gpnmb, consistent with a dietary NASH model. Overall, snSeq distinguished cell-specific transcriptional changes and population shifts consistent with the hepatotoxicity of TCDD.
Publication(s) associated with this dataset:- Nault R, Fader KA, Zacharewski TR. 2021. Single-nuclei RNA sequencing assessment of the hepatic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Cell Mol Gastroenterol Hepatol 11:147-159. doi:10.1016/j.jcmgh.2020.07.012 PMID:32791302 PMCID:PMC7674514