scholarly journals Transcriptional profiling of macrophages derived from monocytes and iPS cells identifies a conserved response to LPS and novel alternative transcription

2015 ◽  
Author(s):  
Kaur Alasoo ◽  
Fernando Martinez Estrada ◽  
Christine Hale ◽  
Siamon Gordon ◽  
Fiona Powrie ◽  
...  
Keyword(s):  
Transcriptional Profiling ◽  
Tissue Remodelling ◽  
Functional Studies ◽  
Expression Of Genes ◽  
Genome Wide ◽  
Individual Transcript ◽  
Alternative Transcription ◽  
A Genome ◽  
Region Usage ◽  
Induced Pluripotent

Macrophages differentiated from human induced pluripotent stem cells (IPSDMs) are a potentially valuable new tool for linking genotype to phenotype in functional studies. However, at a genome-wide level these cells have remained largely uncharacterised. Here, we compared the transcriptomes of naïve and lipopolysaccharide (LPS) stimulated monocyte-derived macrophages (MDMs) and IPSDMs using RNA-Seq. The IPSDM and MDM transcriptomes were broadly similar and exhibited a highly conserved response to LPS. However, there were also significant differences in the expression of genes associated with antigen presentation and tissue remodelling. Furthermore, genes coding for multiple chemokine involved in neutrophil recruitment were more highly expressed in IPSDMs upon LPS stimulation. Additionally, analysing individual transcript expression identified hundreds of genes undergoing alternative promoter and 3′ untranslated region usage following LPS treatment representing a previously under-appreciated level of regulation in the LPS response.

scholarly journals Genome-Wide Analysis of the Stationary-Phase Sigma Factor (Sigma-H) Regulon of Bacillus subtilis

2002 ◽  
Vol 184 (17) ◽  
pp. 4881-4890 ◽  
Author(s):  
Robert A. Britton ◽  
Patrick Eichenberger ◽  
Jose Eduardo Gonzalez-Pastor ◽  
Paul Fawcett ◽  
Rita Monson ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Rna Polymerase ◽  
Stationary Phase ◽  
Sigma Factor ◽  
Transcriptional Profiling ◽  
Open Reading Frames ◽  
Nutrient Sources ◽  
Genome Wide ◽  
A Genome ◽  
Sigma H

ABSTRACT Sigma-H is an alternative RNA polymerase sigma factor that directs the transcription of many genes that function at the transition from exponential growth to stationary phase in Bacillus subtilis. Twenty-three promoters, which drive transcription of 33 genes, are known to be recognized by sigma-H-containing RNA polymerase. To identify additional genes under the control of sigma-H on a genome-wide basis, we carried out transcriptional profiling experiments using a DNA microarray containing >99% of the annotated B. subtilis open reading frames. In addition, we used a bioinformatics-based approach aimed at the identification of promoters recognized by RNA polymerase containing sigma-H. This combination of approaches was successful in confirming most of the previously described sigma-H-controlled genes. In addition, we identified 26 putative promoters that drive expression of 54 genes not previously known to be under the direct control of sigma-H. Based on the known or inferred function of most of these genes, we conclude that, in addition to its previously known roles in sporulation and competence, sigma-H controls genes involved in many physiological processes associated with the transition to stationary phase, including cytochrome biogenesis, generation of potential nutrient sources, transport, and cell wall metabolism.

scholarly journals Expanding the Genetic Architecture of Nicotine Dependence and its Shared Genetics with Multiple Traits: Findings from the Nicotine Dependence GenOmics (iNDiGO) Consortium

2020 ◽  
Author(s):  
Bryan C. Quach ◽  
Michael J. Bray ◽  
Nathan C. Gaddis ◽  
Mengzhen Liu ◽  
Teemu Palviainen ◽  
...  
Keyword(s):  
Nicotine Dependence ◽  
Genetic Architecture ◽  
Genome Wide Association Study ◽  
African Ancestry ◽  
Multiple Traits ◽  
Expression Of Genes ◽  
Genome Wide ◽  
A Genome ◽  
The Uk ◽  
Smoking Index

AbstractCigarette smoking is the leading cause of preventable morbidity and mortality. Knowledge is evolving on genetics underlying initiation, regular smoking, nicotine dependence (ND), and cessation. We performed a genome-wide association study using the Fagerström Test for ND (FTND) in 58,000 smokers of European or African ancestry. Five genome-wide significant loci, including two novel loci MAGI2/GNAI1 (rs2714700) and TENM2 (rs1862416) were identified, and loci reported for other smoking traits were extended to ND. Using the heaviness of smoking index (HSI) in the UK Biobank (N=33,791), rs2714700 was consistently associated, but rs1862416 was not associated, likely reflecting ND features not captured by the HSI. Both variants were cis-eQTLs (rs2714700 for MAGI2-AS3 in hippocampus, rs1862416 for TENM2 in lung), and expression of genes spanning ND-associated variants was enriched in cerebellum. SNP-based heritability of ND was 8.6%, and ND was genetically correlated with 17 other smoking traits (rg=0.40–0.95) and co-morbidities. Our results emphasize the FTND as a composite phenotype that expands genetic knowledge of smoking, including loci specific to ND.

scholarly journals Genomic and functional gene studies suggest a key role of beta-carotene oxygenase 1 like (bco1l) gene in salmon flesh color

2019 ◽  
Author(s):  
Hanna Helgeland ◽  
Marte Sodeland ◽  
Nina Zoric ◽  
Jacob Seilø Torgersen ◽  
Fabian Grammes ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Beta Carotene ◽  
Color Variation ◽  
Flesh Color ◽  
Functional Studies ◽  
Genetic Components ◽  
Genome Wide ◽  
A Genome ◽  
Mrna And Protein Expression

AbstractRed coloration of muscle tissue (flesh) is a unique trait in several salmonid genera, including Atlantic salmon. The color results from dietary carotenoids deposited in the flesh, whereas the color intensity is affected both by diet and genetic components. Herein we report on a genome-wide association study (GWAS) to identify genetic variation underlying this trait. Two SNPs on ssa26 showed strong associations to the flesh color in salmon. Two genes known to be involved in carotenoid metabolism were located in this QTL-region: beta-carotene oxygenase 1 (bco1) and beta-carotene oxygenase 1 like (bco1l). To determine whether flesh color variation is caused by one, or both, of these genes, several functional studies were carried out including mRNA and protein expression in fish with red and pale flesh color. The catalytic abilities of these two genes were also tested with different carotenoids. Our results suggest bco1l to be the most likely gene to explain the flesh color variation observed in this population.

scholarly journals Genome-wide identification, expression profiles and regulatory network of MAPK cascade gene family in barley

2019 ◽  
Author(s):  
Licao Cui ◽  
Guang Yang ◽  
Jali Yan ◽  
Yan Pan ◽  
Xiaojun Nie
Keyword(s):  
Regulatory Network ◽  
Expression Profiles ◽  
Purifying Selection ◽  
Mapk Cascade ◽  
Mitogen Activated Protein Kinase ◽  
Systematic Analysis ◽  
Functional Studies ◽  
Genome Wide ◽  
A Genome ◽  
Duplication Events

Abstract Background Mitogen-activated protein kinase (MAPK) cascade is a conserved and universal signal transduction module in organism. Although it has been well characterized in many plants, no systematic analysis has been conducted in the model cereal crop barley. Results Here, we identified 20 MAPKs, 6 MAPKKs and 156 MAPKKKs through a genome-wide search method using the latest published barley genomic data. Phylogenetic analysis assigned all the MAPK cascade genes into three groups in accordance to MAPK, MAPKK and MAPKKK family. Gene duplication revealed that segmental and tandem duplication events contributed to the expansion of barley MAPK cascade genes and the duplicated gene pairs were found to undergone strong purifying selection. Expression profiles of the HvMAPK, HvMAPKK and HvMAPKKKs were then investigated in different organs and under diverse stresses using the available 132 RNA-seq datasets, and then the tissue-specific and stress-responsive ones were found. Finally, co-expression regulatory network of MAPK cascade genes was constructed by WGCNA tool, resulting in a complicated network composed of a total of 72 branches containing 46 HvMAPK cascade genes and 46 miRNAs. Conclusion This study provides the candidates for further functional studies and also contribute to better understand the MAPK cascade regulatory network in barley and beyond.

scholarly journals Genomic and functional gene studies suggest a key role of beta-carotene oxygenase 1 like (bco1l) gene in salmon flesh color

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hanna Helgeland ◽  
Marte Sodeland ◽  
Nina Zoric ◽  
Jacob Seilø Torgersen ◽  
Fabian Grammes ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Beta Carotene ◽  
Color Variation ◽  
Flesh Color ◽  
Functional Studies ◽  
Genetic Components ◽  
Genome Wide ◽  
A Genome ◽  
Mrna And Protein Expression

AbstractRed coloration of muscle tissue (flesh) is a unique trait in several salmonid genera, including Atlantic salmon. The color results from dietary carotenoids deposited in the flesh, whereas the color intensity is affected both by diet and genetic components. Herein we report on a genome-wide association study (GWAS) to identify genetic variation underlying this trait. Two SNPs on ssa26 showed strong associations to the flesh color in salmon. Two genes known to be involved in carotenoid metabolism were located in this QTL- region: beta-carotene oxygenase 1 (bco1) and beta-carotene oxygenase 1 like (bco1l). To determine whether flesh color variation is caused by one, or both, of these genes, functional studies were carried out including mRNA and protein expression in fish with red and pale flesh color. The catalytic abilities of these two genes were also tested with different carotenoids. Our results suggest bco1l to be the most likely gene to explain the flesh color variation observed in this population.

scholarly journals A genome-wide transcriptional analysis of morphology determination inCandida albicans

2013 ◽  
Vol 24 (3) ◽  
pp. 246-260 ◽  
Author(s):  
Patricia L. Carlisle ◽  
David Kadosh
Keyword(s):  
Gene Expression ◽  
Fungal Infections ◽  
Transcriptional Profiling ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Transcriptional Analysis ◽  
Specific Gene ◽  
Genome Wide ◽  
A Genome ◽  
Genetically Manipulated

Candida albicans, the most common cause of human fungal infections, undergoes a reversible morphological transition from yeast to pseudohyphal and hyphal filaments, which is required for virulence. For many years, the relationship among global gene expression patterns associated with determination of specific C. albicans morphologies has remained obscure. Using a strain that can be genetically manipulated to sequentially transition from yeast to pseudohyphae to hyphae in the absence of complex environmental cues and upstream signaling pathways, we demonstrate by whole-genome transcriptional profiling that genes associated with pseudohyphae represent a subset of those associated with hyphae and are generally expressed at lower levels. Our results also strongly suggest that in addition to dosage, extended duration of filament-specific gene expression is sufficient to drive the C. albicans yeast-pseudohyphal-hyphal transition. Finally, we describe the first transcriptional profile of the C. albicans reverse hyphal-pseudohyphal-yeast transition and demonstrate that this transition involves not only down-regulation of known hyphal-specific, genes but also differential expression of additional genes that have not previously been associated with the forward transition, including many involved in protein synthesis. These findings provide new insight into genome-wide expression patterns important for determining fungal morphology and suggest that in addition to similarities, there are also fundamental differences in global gene expression as pathogenic filamentous fungi undergo forward and reverse morphological transitions.

scholarly journals Genome-Wide Significance for PCLO as a Gene for Major Depressive Disorder

2017 ◽  
Vol 20 (4) ◽  
pp. 267-270 ◽  
Author(s):  
Hamdi Mbarek ◽  
Yuri Milaneschi ◽  
Jouke-Jan Hottenga ◽  
Lannie Ligthart ◽  
Eco J. C. de Geus ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Genome Wide Association Study ◽  
Major Depressive ◽  
Significance Level ◽  
Functional Studies ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Significance

In 2009, the first genome-wide association study (GWAS) for major depressive disorder (MDD) highlighted an association with PCLO locus on chromosome 7, although not reaching genome-wide significance level. In the present study, we revisited the original GWAS after increasing the overall sample size and the number of interrogated SNPs. In an analysis comparing 1,942 cases with lifetime diagnosis of MDD and 4,565 controls, PCLO showed a genome-wide significant association with MDD at SNP (rs2715157, p = 2.91 × 10−8) and gene-based (p = 1.48 × 10−7) level. Our results confirm the potential role of the PCLO gene in MDD, which is worth further replication and functional studies.

scholarly journals Genome-wide CRISPR/Cas9-knockout in human induced Pluripotent Stem Cell (iPSC)-derived macrophages

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elena Navarro-Guerrero ◽  
Chwen Tay ◽  
Justin P. Whalley ◽  
Sally A. Cowley ◽  
Ben Davies ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Genome Engineering ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Loss Of Function ◽  
Lentiviral Transduction ◽  
Genome Wide ◽  
A Genome ◽  
Human Pathology ◽  
Induced Pluripotent

AbstractGenome engineering using CRISPR/Cas9 technology enables simple, efficient and precise genomic modifications in human cells. Conventional immortalized cell lines can be easily edited or screened using genome-wide libraries with lentiviral transduction. However, cell types derived from the differentiation of induced Pluripotent Stem Cells (iPSC), which often represent more relevant, patient-derived models for human pathology, are much more difficult to engineer as CRISPR/Cas9 delivery to these differentiated cells can be inefficient and toxic. Here, we present an efficient, lentiviral transduction protocol for delivery of CRISPR/Cas9 to macrophages derived from human iPSC with efficiencies close to 100%. We demonstrate CRISPR/Cas9 knockouts for three nonessential proof-of-concept genes—HPRT1, PPIB and CDK4. We then scale the protocol and validate for a genome-wide pooled CRISPR/Cas9 loss-of-function screen. This methodology enables, for the first time, systematic exploration of macrophage involvement in immune responses, chronic inflammation, neurodegenerative diseases and cancer progression, using efficient genome editing techniques.

scholarly journals Genome-wide transcriptional profiling uncovers a similar oligodendrocyte-related transcriptional response to acute and chronic alcohol drinking in the amygdala

2021 ◽  
Author(s):  
Sharvari Narendra ◽  
Claudia Klengel ◽  
Bilal Hamzeh ◽  
Drasti Patel ◽  
Joy Otten ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alcohol Drinking ◽  
Brain Area ◽  
Transcriptional Profiling ◽  
Expression Patterns ◽  
Transcriptional Response ◽  
Histone Deacetylation ◽  
Regulatory Pathways ◽  
Genome Wide ◽  
A Genome

AbstractAlcohol intake progressively increases after prolonged consumption of alcohol, but relatively few new therapeutics targeting development of alcohol use disorder (AUD) have been validated. Here, we conducted a genome-wide RNA-sequencing (RNA-seq) analysis in mice exposed to different modes (acute vs chronic) of ethanol drinking. We focused on transcriptional profiles in the amygdala including the central and basolateral subnuclei, a brain area previously implicated in alcohol drinking and seeking, demonstrating distinct gene expression patterns and canonical pathways induced by both acute and chronic intake. Surprisingly, both drinking modes triggered similar transcriptional changes, including up-regulation of ribosome-related/translational pathways and myelination pathways, and down-regulation of chromatin binding and histone modification. Notably, multiple genes that were significantly regulated in mouse amygdala with alcohol drinking, including Atp2b1, Slc4a7, Nfkb1, Nts, and Hdac2, among others had previously been associated with human AUD via GWAS or other genomic studies. In addition, analyses of hub genes and upstream regulatory pathways predicted that voluntary ethanol consumption affects epigenetic changes via histone deacetylation pathways, oligodendrocyte and myelin function, and oligodendrocyte-related transcriptional factor, Sox17.Overall, our results suggest that the transcriptional landscape in the central and basolateral subnuclei of the amygdala is sensitive to voluntary alcohol drinking. They provide a unique resource of gene expression data for future translational studies examining transcriptional mechanisms underlying the development of AUD due to alcohol consumption.

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