Transcriptomics

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Nickel-induced transcriptional memory in lung epithelial cells promotes interferon signaling upon nicotine exposure


ABSTRACT: Nickel is an environmental toxicant prevalent in the atmosphere. Nickel exposure is associated with a multitude of human health hazards including chronic respiratory ailments and lung and nasal cancers. Our earlier studies on nickel exposure in lung cells showed that a majority of the gene expression changes caused by nickel exposure persisted even after termination of exposure (nickel-washed-out cells (NiW)). In this study, we wanted to examine the impact of a secondary toxicant exposure on the nickel-washed-out (NiW) cells as compared to the cells that were never exposed to nickel. To accomplish this, we exposed the untreated control cells (UT) and the nickel-washed-out cells (NiW) to multiple doses of nicotine (NTE). RNA-Seq analysis showed that the exposure of NiW cells to nicotine (NiW-NTE) caused unique gene expression changes that were markedly different from the gene expression changes caused by nicotine exposure of UT cells, which were never exposed to nickel. Analysis of the differentially expressed genes using Reactome Pathway analysis predicted interferon signaling only in the NiW-NTE cells. Upstream Regulator Analysis (URA) predicted STAT-1, a transcription factor that mediates cellular response to interferons, as the top potential upstream regulator in the NiW-NTE cells. Furthermore, chromatin immunoprecipitation (ChIP) analysis revealed increased STAT-1 binding at the promoters of genes associated with interferon signaling in NiW-NTE cells. Aberrant STAT-1 activation has been shown to promote carcinogenesis and interferon signaling promotes pathogenesis of autoimmune disease. Therefore, our results suggest that the epigenetic and transcriptional memory of the cells from the previous nickel exposure could negatively influence the outcome of secondary exposure to nicotine.

ORGANISM(S): Homo sapiens

PROVIDER: GSE242791 | GEO | 2023/11/11

REPOSITORIES: GEO

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