Superfund Research Program
Arsenic and Innate Immunity in Human Lung
Project Leader: Bruce A. Stanton
Grant Number: P42ES007373
Funding Period: 2005-2021
Project-Specific Links
Title: Defining effects of in utero arsenic exposure on immune cells in lungs of adult mice exposed to Influenza A with single cell RNA sequencing
Accession Number: GSE142047
Link to Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE142047
Repository: Gene Expression Omnibus (GEO)
Data Type(s): Gene Expression
Experiment Type(s): Expression profiling by high throughput sequencing
Organism(s): Mus musculus
Summary: Our recent studies have shown that adult mice exposed to inorganic arsenic exclusively in utero (100 ppb via maternal drinking water) exhibit greater lung damage and inflammation following infection with IAV (Influenza A virus, H1N1) than control mice not exposed in utero. We employed an unbiased single cell RNA sequencing approach to conduct a high resolution molecular analysis of recruited immune cells and their transcriptional activities in the lungs of arsenic-exposed and control mice at day 3 after IAV infection. Transcriptional profiling of single immune cells from 6 mice (3 As, 3 Con, all exposed to IAV) revealed evidence of an enhanced inflammatory response mediated by dysregulation of innate immune functions of monocyte derived macrophages, neutrophils and alveolar macrophages. Dams were exposed to 100ppb sodium arsenite or control drinking water from cervical plug formation until pups were born. Arsenic was removed from drinking water and F1 offspring were allowed to mature to adulthood (7-8 weeks). Three F1 adult female mice from each treatment group were randomly selected and infected with 0.5 LD50 of influenza A/PR8/34. Whole lung homogenate was collected at day 3 of infection, and CD45+ immune cells isolated for single cell RNA sequencing (10X Genomics).
Publication(s) associated with this dataset:- Hsu KS, Goodale BC, Ely KH, Hampton TH, Stanton BA, Enelow RI. 2020. Single-cell RNA-seq analysis reveals that prenatal arsenic exposure results in long-term, adverse effects on immune gene expression in response to Influenza A infection. Toxicol Sci 176:312-328. doi:10.1093/toxsci/kfaa080 PMID:32514536 PMCID:PMC7416320