Project description:Data reveal that smokers exhibit distinct gene expression profiles relative to non-smokers and moist snuff consumers. Moist snuff consumer gene expression largely resembles that of non-tobacco consumers. Gene expression profiles were used to identify the effects of combustible (smoking) and non-combustible tobacco (moist snuff) products use.
Project description:Cigarette smoking exerts diverse physiological effects including immune suppression. Existing US epidemiological data show that consumption of smokeless tobacco products, such as moist snuff, is less harmful relative to cigarette smoking. In efforts to understand the molecular changes due to consumption of different tobacco product classes, we have shown recently that smokers exhibit distinct peripheral blood mononuclear cells (PBMCs) gene expression patterns relative to moist snuff users and non-tobacco consumers (NTCs). To better characterize the biological effects exerted from the use of different tobacco products, a genome-wide gene expression study, using a cultured PBMC model, was performed. Global gene expression profiling results showed that 5,421 genes (2,809 upregulated and 2,612 downregulated) were dose-dependently changed by WSCM (pFDR < 0.01). Some gene expression changes detected in the cultured system were also observed in clinical studies. For example, FEZ1 and SLAMF7 were suppressed by WSCM while CCR2 and HHEX genes were upregulated by WSCM commonly in the cultured experiment and clinical studies. WSCM exposures, but not STE, uniquely affected genes involved in immune cell development and inflammatory response. Ingenuity Pathway Analysis identified upstream regulators, such as TNF, IL1β, and NFκB to be likely responsible for the observed gene expression changes and that these cascading signals were generally suppressed by WSCM, but not STE. Collectively, these findings sµggested that combustible and non-combustible tobacco products produce distinct biological effects which could explain the observed chronic immune suppression in smokers.
Project description:Alternations in gene methylation and other epigenetic changes regulate normal development as well as drive disease progression. Chronic cigarette smoking causes hyper- and hypo-methylation of genes that could contribute to smoking-related diseases. It is unclear whether consumers of non-combustible tobacco, such as moist snuff, also exhibit such perturbations in their methylome. Here, we present global methylation changes relative to non-tobacco consumers in buccal cells collected from smokers (SMK) and moist snuff consumers (MSC). Generally healthy adult male study subjects were recruited into SMK, MSC and Non-Tobacco Consumer (NTC) cohorts (40 subjects/cohort). Global methylation profiling was performed on the Illumina 450K methylation array using buccal cell DNA. A total of 1,252 loci were found to be significantly differentially methylated in tobacco consumers relative to non-tobacco consumers. Overall, the SMK cohort exhibited larger qualitative and quantitative changes relative to MSC. Approximately half of the total number of gene loci, classified as Combustible Tobacco-Related signatures, and a third of the changes, termed Tobacco-Related signatures, were commonly detected in the tobacco consumers. Very few differences were detected between MSC and NTC, and hierarchical clustering of the top 50 significant gene loci suggested that MSC and NTC co-cluster. Consistent with physiological functions of AhR, combustible tobacco drives profound changes in buccal cell methylation status, principally impacting cell development and immune response pathways. These results aid in placing combustible and non-combustible tobacco products along a risk continuum and provide additional insights into the effects of tobacco consumption.
Project description:Cigarette smoking exerts diverse physiological effects including immune suppression. Existing US epidemiological data show that consumption of smokeless tobacco products, such as moist snuff, is less harmful relative to cigarette smoking. In efforts to understand the molecular changes due to consumption of different tobacco product classes, we have shown recently that smokers exhibit distinct peripheral blood mononuclear cells (PBMCs) gene expression patterns relative to moist snuff users and non-tobacco consumers (NTCs). To better characterize the biological effects exerted from the use of different tobacco products, a genome-wide gene expression study, using a cultured PBMC model, was performed. Gene expression profiles from PBMCs treated with low equi-nicotine units (0.3 µg/ml) of WS-CM and a single high dose of STE (100 µg/ml) were similar to those from untreated controls. Cells treated with medium and high equi-nicotine unit doses of WS-CM (1.0 and 3.0 µg/ml) exhibited significantly different gene expression profiles compared to the low equi-nicotine WS-CM dose and STE. Pre-treatment with higher doses of WS-CM inhibited the expression of several pro-inflammatory genes that regulate immune responses, including IFNγ, TNFα, and IL-2. Gene expression changes of these genes and other cytokine signaling genes were confirmed by qRT-PCR. Moreover, secretion of IFNγ, TNFα and IL-2 proteins was abolished by WS-CM pre-treatment even after 24 hours of toll like receptor stimulation. Additionally, pathway analyses revealed that higher doses of WS-CM inhibited NF-ĸβ signaling and a wide range of signaling pathways associated with immune cell differentiation and inflammatory responses, and increased expression of genes involved in apoptosis. Collectively, our results show that pre-treatment of PBMCs with higher doses of WS-CM inhibits immune activation and effector cytokine expression and secretion, resulting in a reduced immune response, whereas STE had minimal effect.
2019-09-25 | GSE127977 | GEO
Project description:Shotgun metagenome and metatranscriptome of commercial smokeless tobacco moist snuff tobacco product from USA
Project description:Selective breeding of domestic dogs has generated diverse breeds often optimized for performing specialized tasks. Despite the heritability of breed-typical behavioral traits, identification of causal loci has proven challenging due to the complexity of canine population structure. We overcome longstanding difficulties in identifying genetic drivers of canine behavior by developing an innovative framework for understanding relationships between breeds and the behaviors that define them utilizing genetic data for over 4,000 domestic, semi-feral and wild canids and behavioral survey data for over 46,000 dogs. We identify ten major canine genetic lineages and their behavioral correlates and show that breed diversification is predominantly driven by non-coding regulatory variation. We determine that lineage-associated genes converge in neurodevelopmental co-expression networks, identifying a sheepdog-associated enrichment for interrelated axon guidance functions. This work presents a scaffold for canine diversification that positions the domestic dog as an unparalleled system for revealing the genetic origins of behavioral diversity.
Project description:We have completed the high quality reference genome for domestic sheep (Oar v3.1) and performed a detailed survey of gene expression across different tissues. RNA-seq data of 7 tissue types from the reference female Texel and skin tissue from a Gansu alpine fine wool sheep were sequenced.