Combined Transcriptomic Analysis Revealed AKR1B10 Played an Important Role in Psoriasis through the Dysregulated Lipid Pathway and Overproliferation of Keratinocyte

RNA-seq has enabled in-depth analysis of the pathogenesis of psoriasis on the transcriptomic level, and many biomarkers have been discovered to be related to the immune response, lipid metabolism, and keratinocyte proliferation. However, few studies have combined analysis from various datasets. In this study, we integrated different psoriasis RNA-seq datasets to reveal the pathogenesis of psoriasis through the analysis of differentially expressed genes (DEGs), pathway analysis, and functional annotation. The revealed biomarkers were further validated through proliferation phenotypes. The results showed that DEGs were functionally related to lipid metabolism and keratinocyte differentiation dysregulation. The results also showed new biomarkers, such as AKR1B10 and PLA2G gene families, as well as pathways that include the PPAR signaling pathway, cytokine-cytokine receptor interaction, alpha-linoleic acid metabolism, and glycosphingolipid biosynthesis. Using siRNA knockdown assays, we further validated the role that the AKR1B10 gene plays in proliferation. Our study demonstrated not only the dysfunction of the AKR1B10 gene in lipid metabolizing but also its important role in the overproliferation and migration of keratinocyte, which provided evidence for further therapeutic uses for psoriasis.

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The Impact of the Deepwater Horizon Oil Spill upon Lung Health—Mouse Model-Based RNA-Seq Analyses

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17155466 ◽

2020 ◽

Vol 17 (15) ◽

pp. 5466

Author(s):

Yao-Zhong Liu ◽

Charles A Miller ◽

Yan Zhuang ◽

Sudurika S Mukhopadhyay ◽

Shigeki Saito ◽

...

Keyword(s):

Lung Tumor ◽

Left Lung ◽

Receptor Interaction ◽

Rna Seq ◽

Kegg Pathways ◽

Corexit 9500 ◽

P53 Signaling ◽

Oropharyngeal Aspiration ◽

Transcriptomic Level ◽

The Impact

We used a transcriptomic approach to interrogate the effects of a saline-accommodated fraction from the Macondo 252 well (MC252) oil and Corexit dispersants on lung tissue. Wild-type C57BL/6 male and female mice were exposed on days 0, 7 and 13 by oropharyngeal aspiration to saline accommodated fractions (SAF) of crude oil from the Macondo (MC252) well, Corexit 9500, Corexit 9527, 9500+oil and 9527+oil or a saline solution as the vehicle control. These treatments did not cause overt toxicity, with the exception of the Corexit exposures which caused brief weight loss after the first exposure. On day 14, total RNA was isolated from the left lung for RNA-seq analyses. KEGG-pathway-based differential expression revealed that Corexit 9527 elicited the strongest changes involving the upregulation of 19 KEGG pathways (FDR < 0.10), followed by Corexit 9500 with the upregulation of seven pathways (FDR < 0.10). As an important signature, pathways related to a response to DNA damage (e.g., p53 signaling and mismatch repair) dominate those upregulated by Corexit 9527 and Corexit 9500. In addition, pro-inflammatory pathways (e.g., cytokine-cytokine receptor interaction, IL-17 signaling pathway and TNF signaling pathways) were upregulated selectively in oil-treated male mice. Surprisingly, oil + dispersant combinations caused lesser effects than the individual treatments at the transcriptomic level. Overall, these findings support potential genotoxicity, inflammation and cell death due to dispersant or oil exposures. Similar exposures to lung tumor bearing K-RasLA1 mice provided evidence for tumor promotion by oil and Corexit dispersant treatments. Our mouse RNA-seq analyses may be relevant to the pulmonary health hazards of MC252 oil and dispersants experienced in exposed populations.

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Identification and Expression Analysis of the Genes Involved in the Raffinose Family Oligosaccharides Pathway of Phaseolus vulgaris and Glycine max

Plants ◽

10.3390/plants10071465 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1465

Author(s):

Ramon de Koning ◽

Raphaël Kiekens ◽

Mary Esther Muyoka Toili ◽

Geert Angenon

Keyword(s):

Common Bean ◽

Seed Development ◽

Expression Analysis ◽

De Novo ◽

Expression Patterns ◽

Gene Families ◽

Rna Seq ◽

Raffinose Family Oligosaccharides ◽

Specific Expression ◽

Raffinose Synthase

Raffinose family oligosaccharides (RFO) play an important role in plants but are also considered to be antinutritional factors. A profound understanding of the galactinol and RFO biosynthetic gene families and the expression patterns of the individual genes is a prerequisite for the sustainable reduction of the RFO content in the seeds, without compromising normal plant development and functioning. In this paper, an overview of the annotation and genetic structure of all galactinol- and RFO biosynthesis genes is given for soybean and common bean. In common bean, three galactinol synthase genes, two raffinose synthase genes and one stachyose synthase gene were identified for the first time. To discover the expression patterns of these genes in different tissues, two expression atlases have been created through re-analysis of publicly available RNA-seq data. De novo expression analysis through an RNA-seq study during seed development of three varieties of common bean gave more insight into the expression patterns of these genes during the seed development. The results of the expression analysis suggest that different classes of galactinol- and RFO synthase genes have tissue-specific expression patterns in soybean and common bean. With the obtained knowledge, important galactinol- and RFO synthase genes that specifically play a key role in the accumulation of RFOs in the seeds are identified. These candidate genes may play a pivotal role in reducing the RFO content in the seeds of important legumes which could improve the nutritional quality of these beans and would solve the discomforts associated with their consumption.

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Transcriptome profiling of the diaphragm in a controlled mechanical ventilation model reveals key genes involved in ventilator-induced diaphragmatic dysfunction

BMC Genomics ◽

10.1186/s12864-021-07741-9 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Ruining Liu ◽

Gang Li ◽

Haoli Ma ◽

Xianlong Zhou ◽

Pengcheng Wang ◽

...

Keyword(s):

Mechanical Ventilation ◽

Signaling Pathway ◽

Wistar Rats ◽

Cholesterol Metabolism ◽

Expression Profiles ◽

Receptor Interaction ◽

Pathophysiological Mechanism ◽

Rna Seq ◽

Diaphragmatic Dysfunction ◽

Controlled Mechanical Ventilation

Abstract Background Ventilator-induced diaphragmatic dysfunction (VIDD) is associated with weaning difficulties, intensive care unit hospitalization (ICU), infant mortality, and poor long-term clinical outcomes. The expression patterns of long noncoding RNAs (lncRNAs) and mRNAs in the diaphragm in a rat controlled mechanical ventilation (CMV) model, however, remain to be investigated. Results The diaphragms of five male Wistar rats in a CMV group and five control Wistar rats were used to explore lncRNA and mRNA expression profiles by RNA-sequencing (RNA-seq). Muscle force measurements and immunofluorescence (IF) staining were used to verify the successful establishment of the CMV model. A total of 906 differentially expressed (DE) lncRNAs and 2,139 DE mRNAs were found in the CMV group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to determine the biological functions or pathways of these DE mRNAs. Our results revealed that these DE mRNAs were related mainly related to complement and coagulation cascades, the PPAR signaling pathway, cholesterol metabolism, cytokine-cytokine receptor interaction, and the AMPK signaling pathway. Some DE lncRNAs and DE mRNAs determined by RNA-seq were validated by quantitative real-time polymerase chain reaction (qRT-PCR), which exhibited trends similar to those observed by RNA-sEq. Co-expression network analysis indicated that three selected muscle atrophy-related mRNAs (Myog, Trim63, and Fbxo32) were coexpressed with relatively newly discovered DE lncRNAs. Conclusions This study provides a novel perspective on the molecular mechanism of DE lncRNAs and mRNAs in a CMV model, and indicates that the inflammatory signaling pathway and lipid metabolism may play important roles in the pathophysiological mechanism and progression of VIDD.

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Genome-Wide Identification and Characterization of Hsf and Hsp Gene Families and Gene Expression Analysis under Heat Stress in Eggplant (Solanum melongema L.)

Horticulturae ◽

10.3390/horticulturae7060149 ◽

2021 ◽

Vol 7 (6) ◽

pp. 149

Author(s):

Chao Gong ◽

Qiangqiang Pang ◽

Zhiliang Li ◽

Zhenxing Li ◽

Riyuan Chen ◽

...

Keyword(s):

Heat Stress ◽

Gene Families ◽

High Temperature Stress ◽

Pcr Analysis ◽

Rna Seq ◽

Genome Wide ◽

Motif Composition ◽

Hsp Genes ◽

Identification And Characterization

Under high temperature stress, a large number of proteins in plant cells will be denatured and inactivated. Meanwhile Hsfs and Hsps will be quickly induced to remove denatured proteins, so as to avoid programmed cell death, thus enhancing the thermotolerance of plants. Here, a comprehensive identification and analysis of the Hsf and Hsp gene families in eggplant under heat stress was performed. A total of 24 Hsf-like genes and 117 Hsp-like genes were identified from the eggplant genome using the interolog from Arabidopsis. The gene structure and motif composition of Hsf and Hsp genes were relatively conserved in each subfamily in eggplant. RNA-seq data and qRT-PCR analysis showed that the expressions of most eggplant Hsf and Hsp genes were increased upon exposure to heat stress, especially in thermotolerant line. The comprehensive analysis indicated that different sets of SmHsps genes were involved downstream of particular SmHsfs genes. These results provided a basis for revealing the roles of SmHsps and SmHsp for thermotolerance in eggplant, which may potentially be useful for understanding the thermotolerance mechanism involving SmHsps and SmHsp in eggplant.

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Neuromuscular junction-specific genes screening by deep RNA-seq analysis

Cell & Bioscience ◽

10.1186/s13578-021-00590-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tiankun Hui ◽

Hongyang Jing ◽

Xinsheng Lai

Keyword(s):

Ion Channel ◽

Neuromuscular Junctions ◽

Gene Set Enrichment Analysis ◽

Differentially Expressed ◽

Muscle Membrane ◽

Receptor Interaction ◽

Specific Gene ◽

Rna Seq ◽

Channel Activity ◽

Ppi Networks

Abstract Background Neuromuscular junctions (NMJs) are chemical synapses formed between motor neurons and skeletal muscle fibers and are essential for controlling muscle contraction. NMJ dysfunction causes motor disorders, muscle wasting, and even breathing difficulties. Increasing evidence suggests that many NMJ disorders are closely related to alterations in specific gene products that are highly concentrated in the synaptic region of the muscle. However, many of these proteins are still undiscovered. Thus, screening for NMJ-specific proteins is essential for studying NMJ and the pathogenesis of NMJ diseases. Results In this study, synaptic regions (SRs) and nonsynaptic regions (NSRs) of diaphragm samples from newborn (P0) and adult (3-month-old) mice were used for RNA-seq. A total of 92 and 182 genes were identified as differentially expressed between the SR and NSR in newborn and adult mice, respectively. Meanwhile, a total of 1563 genes were identified as differentially expressed between the newborn SR and adult SR. Gene Ontology (GO) enrichment analyses, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and gene set enrichment analysis (GSEA) of the DEGs were performed. Protein–protein interaction (PPI) networks were constructed using STRING and Cytoscape. Further analysis identified some novel proteins and pathways that may be important for NMJ development, maintenance and maturation. Specifically, Sv2b, Ptgir, Gabrb3, P2rx3, Dlgap1 and Rims1 may play roles in NMJ development. Hcn1 may localize to the muscle membrane to regulate NMJ maintenance. Trim63, Fbxo32 and several Asb family proteins may regulate muscle developmental-related processes. Conclusion Here, we present a complete dataset describing the spatiotemporal transcriptome changes in synaptic genes and important synaptic pathways. The neuronal projection-related pathway, ion channel activity and neuroactive ligand-receptor interaction pathway are important for NMJ development. The myelination and voltage-gated ion channel activity pathway may be important for NMJ maintenance. These data will facilitate the understanding of the molecular mechanisms underlying the development and maintenance of NMJ and the pathogenesis of NMJ disorders.

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RNA Sequencing (RNA-Seq) Based Transcriptome Analysis in Immune Response of Holstein Cattle to Killed Vaccine against Bovine Viral Diarrhea Virus Type I

Animals ◽

10.3390/ani10020344 ◽

2020 ◽

Vol 10 (2) ◽

pp. 344 ◽

Cited By ~ 3

Author(s):

Bryan Irvine Lopez ◽

Kier Gumangan Santiago ◽

Donghui Lee ◽

Seungmin Ha ◽

Kangseok Seo

Keyword(s):

Immune Response ◽

Enrichment Analysis ◽

Receptor Interaction ◽

Type I ◽

Rna Seq ◽

Diarrhea Virus ◽

Viral Diarrhea ◽

Kegg Pathways ◽

Viral Diarrhea Virus

Immune response of 107 vaccinated Holstein cattle was initially obtained prior to the ELISA test. Five cattle with high and low bovine viral diarrhea virus (BVDV) type I antibody were identified as the final experimental animals. Blood samples from these animals were then utilized to determine significant differentially expressed genes (DEGs) using the RNA-seq transcriptome analysis and enrichment analysis. Our analysis identified 261 DEGs in cattle identified as experimental animals. Functional enrichment analysis in gene ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed the DEGs potentially induced by the inactivated BVDV type I vaccine, and might be responsible for the host immune responses. Our findings suggested that inactivated vaccine induced upregulation of genes involved in different GO annotations, including antigen processing and presentation of peptide antigen (via MHC class I), immune response, and positive regulation of interferon-gamma production. The observed downregulation of other genes involved in immune response might be due to inhibition of toll-like receptors (TLRs) by the upregulation of the Bcl-3 gene. Meanwhile, the result of KEGG pathways revealed that the majority of DEGs were upregulated and enriched to different pathways, including cytokine-cytokine receptor interaction, platelet activation, extracellular matrix (ECM) receptor interaction, hematopoietic cell lineage, and ATP-binding cassette (ABC) transporters. These significant pathways supported our initial findings and are known to play a vital role in shaping adaptive immunity against BVDV type 1. In addition, type 1 diabetes mellitus pathways tended to be significantly enriched. Thus, further studies are needed to investigate the prevalence of type 1 diabetes mellitus in cattle vaccinated with inactivated and live BVDV vaccine.

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Whole Transcriptome Analysis of Hypertension Induced Cardiac Injury Using Deep Sequencing

Cellular Physiology and Biochemistry ◽

10.1159/000438659 ◽

2016 ◽

Vol 38 (2) ◽

pp. 670-682 ◽

Cited By ~ 4

Author(s):

Tao-Tao Li ◽

Xiao-Yan Li ◽

Li-Xin Jia ◽

Jing Zhang ◽

Wen-Mei Zhang ◽

...

Keyword(s):

Transcriptome Analysis ◽

Cell Activation ◽

Critical Role ◽

Cardiac Injury ◽

Interaction Network ◽

Receptor Interaction ◽

Rna Seq ◽

Cardiac Inflammation ◽

Molecular Events ◽

Focal Adhesion Protein

Background/Aims: Hypertension plays a critical role in the cardiac inflammation and injury. However, the mechanism of how hypertension causes the cardiac injury at a molecular level remains to be elucidated. Methods: RNA-Seq has been demonstrated to be an effective approach for transcriptome analysis, which is essential to reveal the molecular constituents of cells and tissues. In this study, we investigated the global molecular events associated with the mechanism of hypertension induced cardiac injury using RNA-Seq analysis. Results: Our results showed that totally 1,801 genes with different expression variations were identified after Ang II infusion at 1, 3 and 7 days. Go analysis showed that the top 5 high enrichment Go terms were response to stress, response to wounding, cellular component organization, cell activation and defense response. KEGG pathway analysis revealed the top 5 significantly overrepresented pathways were associated with ECM-receptor interaction, focal adhesion, protein digestion and absorption, phagosome and asthma. Moreover, protein-protein interaction network analysis indicated that ubiquitin C may play a key role in the processes of hypertension-induced cardiac injury. Conclusion: Our study provides a comprehensive understanding of the transcriptome events in hypertension-induced cardiac pathology.

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Oogenesis and lipid metabolism in the deep-sea sponge Phakellia ventilabrum: an histological, lipidomic and transcriptomic approach

10.21203/rs.3.rs-608731/v1 ◽

2021 ◽

Author(s):

Vasiliki Koutsouveli ◽

David Balgoma ◽

Antonia Checa ◽

Mikael Hedeland ◽

Ana Riesgo ◽

...

Keyword(s):

Fatty Acid ◽

Lipid Metabolism ◽

Deep Sea ◽

Expression Patterns ◽

Rna Seq ◽

Beta Oxidation ◽

Animal Reproduction ◽

Physiological Processes ◽

Key Species ◽

Fatty Acid Beta Oxidation

Abstract Background Sponges contain an astounding diversity of lipids which serve in several biological functions, including yolk formation in their oocytes and the embryos. On animal reproduction, lipids constitute one of the main energy storage forms for the adult and the offspring. The study of lipid metabolism during reproduction can provide information on food-web dynamics and energetic needs of the populations in their habitats, however, there are no studies focusing on the lipid metabolism of sponges during seasonal reproduction. The deep-sea sponge Phakellia ventilabrum (Demospongiae, Bubarida) is a key species of North-Atlantic sponge grounds, but its reproductive biology is not known. In this study, we used histological sections, lipidome profiling (UHPLC-MS), and transcriptomic analysis (RNA-seq) with goal to i. assess the reproductive strategy and seasonality of this species, ii. examine the relative changes in the lipidome signal, and the gene expression patterns (RNA-seq) of enzymes participating in lipid metabolism in female specimens during gametogenesis.Results P. ventilabrum is an oviparous and most certainly gonochoristic species, reproducing in May and September in the different studied areas. Half of specimens were reproducing, generating two to five oocytes per mm2. Oocytes accumulated both protein and lipid droplets. As oogenesis progressed, the signal of most of the unsaturated and monounsaturated triacylglycerides increased, as well as of few other phospholipids. Most of the other lipids and especially those with > 3 unsaturations showed a decrease in signal during the oocyte maturation. In parallel, we detected upregulated genes in female tissues related to triacylglyceride biosynthesis and others related to fatty acid beta-oxidation.Conclusions Triacylglycerides are probably the main type of lipid forming the yolk since this lipid category has the most marked changes, while some other phospholipids may also have a role in oogenesis. In parallel, other lipid categories were oxidized, leading to fatty acid beta-oxidation to cover the energy requirements of female individuals during oogenesis. Variations in the signal of most lipids between the different locations and months suggest that sponges, apart from their own mechanisms of lipid biosynthesis, exploit the food availability in their surroundings to cover the energetic demands in their physiological processes.

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Synovial Gene Signatures Associated with the Development of Rheumatoid Arthritis in At Risk Individuals: a Prospective Study

10.1101/2021.04.27.440770 ◽

2021 ◽

Author(s):

Lisa G.M. van Baarsen ◽

Tineke A. de Jong ◽

Maria J.H. de Hair ◽

Johanna F. Semmelink ◽

Ivy Y. Choi ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

At Risk ◽

Immune Response ◽

Lipid Metabolism ◽

Synovial Tissue ◽

Gene Set Enrichment Analysis ◽

Receptor Interaction ◽

Discovery Cohort ◽

Molecular Changes

AbstractBackgroundPrevious work has shown subtle infiltration of synovial T cells in the absence of overt synovial inflammation in individuals at risk of developing rheumatoid arthritis (RA).ObjectiveTo study the molecular changes in synovium preceding arthritis development in at risk individuals.Materials and methodsWe included sixty-seven individuals with arthralgia who were IgM rheumatoid factor (RF) and/or anti-citrullinated protein antibody (ACPA) positive and without any evidence of arthritis. All individuals underwent mini-arthroscopic synovial tissue sampling of a knee joint at baseline and were followed prospectively. An explorative genome-wide transcriptional profiling study was performed on synovial tissue using Agilent arrays (discovery cohort). Survival analysis was used to identify transcripts associated with arthritis after follow up. Expression levels of differentially expressed genes were validated using quantitative real-time PCR (qPCR). Immunohistochemistry was used to study gene candidates at the protein level in situ.ResultsIn the discovery cohort, 6 of the 13 at risk individuals developed RA after a median follow-up time of 20 months (IQR 2 – 44; pre-RA). The 7 individuals who did not develop RA had a median follow-up time of 85 months (IQR 69 – 86). Using a False Discovery Rate of <5% we found increased expression of 3,151 transcripts correlating with a higher risk of arthritis development, whereas increased expression of 2,437 transcripts correlated with a lower risk. Gene set enrichment analysis revealed that synovial biopsies of pre-RA individuals display higher expression of genes involved in several immune response-related pathways compared with biopsies of individuals who did not develop RA. In contrast, lower expression was observed for genes involved in extracellular matrix receptor interaction, Wnt-mediated signal transduction and lipid metabolism. Two-way hierarchical cluster analysis of 27 genes measured by qPCR classified the synovial biopsies of 61 individuals into two groups, where pre-RA individuals (n=16) showed a preference to cluster together. Synovial tissue from pre-RA individuals were more likely to show podoplanin positive cells and lower lipid staining compared with synovial tissue from individuals who did not develop RA.ConclusionMolecular changes can be detected in synovial tissues before clinical onset of arthritis. Alterations in the immune response genes and lipid metabolism are associated with development of arthritis.

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CStone: A de novo transcriptome assembler for short-read data that identifies non-chimeric contigs based on underlying graph structure

PLoS Computational Biology ◽

10.1371/journal.pcbi.1009631 ◽

2021 ◽

Vol 17 (11) ◽

pp. e1009631

Author(s):

Raquel Linheiro ◽

John Archer

Keyword(s):

De Novo ◽

Simulated Data ◽

Real Data ◽

Gene Families ◽

Classification Systems ◽

Whole Body ◽

Cdna Libraries ◽

Sequence Information ◽

Rna Seq ◽

High Quality

With the exponential growth of sequence information stored over the last decade, including that of de novo assembled contigs from RNA-Seq experiments, quantification of chimeric sequences has become essential when assembling read data. In transcriptomics, de novo assembled chimeras can closely resemble underlying transcripts, but patterns such as those seen between co-evolving sites, or mapped read counts, become obscured. We have created a de Bruijn based de novo assembler for RNA-Seq data that utilizes a classification system to describe the complexity of underlying graphs from which contigs are created. Each contig is labelled with one of three levels, indicating whether or not ambiguous paths exist. A by-product of this is information on the range of complexity of the underlying gene families present. As a demonstration of CStones ability to assemble high-quality contigs, and to label them in this manner, both simulated and real data were used. For simulated data, ten million read pairs were generated from cDNA libraries representing four species, Drosophila melanogaster, Panthera pardus, Rattus norvegicus and Serinus canaria. These were assembled using CStone, Trinity and rnaSPAdes; the latter two being high-quality, well established, de novo assembers. For real data, two RNA-Seq datasets, each consisting of ≈30 million read pairs, representing two adult D. melanogaster whole-body samples were used. The contigs that CStone produced were comparable in quality to those of Trinity and rnaSPAdes in terms of length, sequence identity of aligned regions and the range of cDNA transcripts represented, whilst providing additional information on chimerism. Here we describe the details of CStones assembly and classification process, and propose that similar classification systems can be incorporated into other de novo assembly tools. Within a related side study, we explore the effects that chimera’s within reference sets have on the identification of differentially expression genes. CStone is available at: https://sourceforge.net/projects/cstone/.

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