Genome wide study of adult microglia in Specific-pathogen-free (SPF) mice treated or not during one week with antibiotics (ABX) in males and females.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE108045 | GEO | 2017/12/14
SECONDARY ACCESSION(S): PRJNA422281
REPOSITORIES: GEO
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Project description:Genome wide study of adult microglia in Specific-pathogen-free (SPF) mice treated or not during one week with antibiotics (ABX) in males and females.
| PRJNA422281 | ENA
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Project description:The clearance of apoptotic cells, termed efferocytosis, is essential for tissue homeostasis and prevention of autoimmunity. Although past studies have elucidated local molecular signals that regulate homeostatic efferocytosis1 in a tissue, whether signals arising distally also regulate homeostatic efferocytosis remains elusive. Here, we find that large peritoneal macrophages (LPMs) display impaired efferocytosis in broad-spectrum antibiotics (ABX)-treated, vancomycin-treated, and germ-free mice in vivo. Mechanistically, the microbiota-derived short-chain fatty acid butyrate directly boosted efferocytosis efficiency/capacity in mouse and human macrophages, and rescued ABX-induced LPM efferocytosis defects in vivo. Bulk mRNA sequencing of butyrate-treated macrophages in vitro and single cell mRNA sequencing of LPMs isolated from ABX-treated and butyrate-rescued mice revealed regulation of efferocytosis-supportive transcriptional programs. Specifically, we found that the efferocytosis receptor T-cell immunoglobulin and mucin domain containing 4 (TIM-4, Timd4) was downregulated in LPMs of ABX-treated mice but rescued by oral butyrate and TIM-4 was required for the butyrate-induced enhancement of LPM efferocytosis capacity. LPM efferocytosis was impaired beyond withdrawal of ABX and ABX-treated mice exhibited significantly worse disease in a mouse model of lupus. Our results demonstrate that homeostatic efferocytosis relies on distal metabolic signals and suggest that defective homeostatic efferocytosis may explain link between ABX use and inflammatory disease.
2024-07-16 | GSE270512 | GEO
Project description:Liver plays major roles in vital functions including responses to energy deprivation. It is known that body composition and fuel metabolism differs between genders. However there are many unclear aspects related to metabolic pathways affected by feeding level and gender, which could be addressed by transcriptome analyses. To date, no published study in porcine liver has investigated the effects of both gender and feeding level on global gene expression level.We performed a gene expression analysis, using microarrays, in hepatic samples of pigs of the obese Iberian breed to analyze feeding level and gender effects. Results showed that feeding level leads to small expression differences, while gender leads to larger ones. Biological interpretation of the differentially expressed genes conditional on feeding level showed an overrepresentation of genes implicated in general metabolic processes, responses to stimulus and stress, oxidoreductase activity, calcium ion binding and lipid, organic acid and carbohydrate metabolisms. We validated the expression difference of PHYHD1 by qRT-PCR; however we could not validate the expression differences of other relevant genes. Curiously, validation of PGK1, considered reference gene, confirmed expression differences conditional on feeding level and gender. The annotation of the differentially expressed probes for gender effect allowed to observe sex-chromosome enrichment and dosage compensation phenomena in liver. Biological interpretation showed overrepresentation of genes related with oxidoreductase and transferase activities, lipid, organic acid, carbohydrate and steroid metabolisms and genes related with metabolites generation and energy and electron transport. Aside from 13 consistently across tissue differentially expressed genes between gender, gender hepatic expression dimorphism of key genes involved in lipid, carbohydrate and protein metabolisms and antioxidant capacity were also detected. A deeper qRT-PCR analysis showed a downregulation in entire males of all major genes implicated in hepatic degradation processes of androstenone and skatole. We have identified changes in hepatic gene expression conditional on feeding and gender. Reduction of around 25% in feeding level do not lead to great differences but gender effect leads not only to a larger number of differentially expressed probes, but much larger expression differences. Validation of microarray results is needed mainly for small expression differences.
2009-07-24 | GSE17309 | GEO
Project description:The clearance of apoptotic cells, termed efferocytosis, is essential for tissue homeostasis and prevention of autoimmunity. Although past studies have elucidated local molecular signals that regulate homeostatic efferocytosis1 in a tissue, whether signals arising distally also regulate homeostatic efferocytosis remains elusive. Here, we find that large peritoneal macrophages (LPMs) display impaired efferocytosis in broad-spectrum antibiotics (ABX)-treated, vancomycin-treated, and germ-free mice in vivo. Mechanistically, the microbiota-derived short-chain fatty acid butyrate directly boosted efferocytosis efficiency/capacity in mouse and human macrophages, and rescued ABX-induced LPM efferocytosis defects in vivo. Bulk mRNA sequencing of butyrate-treated macrophages in vitro and single cell mRNA sequencing of LPMs isolated from ABX-treated and butyrate-rescued mice revealed regulation of efferocytosis-supportive transcriptional programs. Specifically, we found that the efferocytosis receptor T-cell immunoglobulin and mucin domain containing 4 (TIM-4, Timd4) was downregulated in LPMs of ABX-treated mice but rescued by oral butyrate and TIM-4 was required for the butyrate-induced enhancement of LPM efferocytosis capacity. LPM efferocytosis was impaired beyond withdrawal of ABX and ABX-treated mice exhibited significantly worse disease in a mouse model of lupus. Our results demonstrate that homeostatic efferocytosis relies on distal metabolic signals and suggest that defective homeostatic efferocytosis may explain link between ABX use and inflammatory disease.
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Project description:Wild-type laboratory strains of model organisms are typically kept in isolation for many years, with the action of genetic drift and selection on mutational variation causing lineages to diverge with time. Natural populations from which such strains are established, show that gender-specific interactions in particular drive many aspects of sequence level and transcriptional level variation. Here, our goal was to identify genes that display transcriptional variation between laboratory strains of Drosophila melanogaster, and to explore evidence of gender-biased interactions underlying that variability. Experiment Overall Design: Three replicate groups of males and virgin females were collected for each sex and genotype combination. Total RNA was extracted independently for each of the 30 samples (five lines x two sexes x three replicates)
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Project description:Liver plays major roles in vital functions including responses to energy deprivation. It is known that body composition and fuel metabolism differs between genders. However there are many unclear aspects related to metabolic pathways affected by feeding level and gender, which could be addressed by transcriptome analyses. To date, no published study in porcine liver has investigated the effects of both gender and feeding level on global gene expression level.We performed a gene expression analysis, using microarrays, in hepatic samples of pigs of the obese Iberian breed to analyze feeding level and gender effects. Results showed that feeding level leads to small expression differences, while gender leads to larger ones. Biological interpretation of the differentially expressed genes conditional on feeding level showed an overrepresentation of genes implicated in general metabolic processes, responses to stimulus and stress, oxidoreductase activity, calcium ion binding and lipid, organic acid and carbohydrate metabolisms. We validated the expression difference of PHYHD1 by qRT-PCR; however we could not validate the expression differences of other relevant genes. Curiously, validation of PGK1, considered reference gene, confirmed expression differences conditional on feeding level and gender. The annotation of the differentially expressed probes for gender effect allowed to observe sex-chromosome enrichment and dosage compensation phenomena in liver. Biological interpretation showed overrepresentation of genes related with oxidoreductase and transferase activities, lipid, organic acid, carbohydrate and steroid metabolisms and genes related with metabolites generation and energy and electron transport. Aside from 13 consistently across tissue differentially expressed genes between gender, gender hepatic expression dimorphism of key genes involved in lipid, carbohydrate and protein metabolisms and antioxidant capacity were also detected. A deeper qRT-PCR analysis showed a downregulation in entire males of all major genes implicated in hepatic degradation processes of androstenone and skatole. We have identified changes in hepatic gene expression conditional on feeding and gender. Reduction of around 25% in feeding level do not lead to great differences but gender effect leads not only to a larger number of differentially expressed probes, but much larger expression differences. Validation of microarray results is needed mainly for small expression differences. Experiment Overall Design: Eight liver samples from eight animals at slaughter, 211 days old, four males and four females, four under high feeding level and four under 25% restriction.
2009-08-07 | E-GEOD-17309 | biostudies-arrayexpress
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