scholarly journals Transcriptome profiling of ulcerative colitis mouse model suggests biomarkers and therapeutic targets for human colitis

2020 ◽  
Author(s):  
Reza Yarani ◽  
Oana Palasca ◽  
Nadezhda T. Doncheva ◽  
Christian Anthon ◽  
Bartosz Pilecki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Mouse Model ◽  
High Throughput ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Unknown Etiology ◽  
Small Rna Sequencing ◽  
Complex Nature

1.AbstractBACKGROUND & AIMSUlcerative colitis (UC) is an inflammatory bowel disorder with unknown etiology. Given its complex nature, in vivo studies to investigate its pathophysiology is vital. Animal models play an important role in molecular profiling necessary to pinpoint mechanisms that contribute to human disease. Thus, we aim to identify common conserved gene expression signatures and differentially regulated pathways between human UC and a mouse model hereof, which can be used to identify UC patients from healthy individuals and to suggest novel treatment targets and biomarker candidates.METHODSTherefore, we performed high-throughput total and small RNA sequencing to comprehensively characterize the transcriptome landscape of the most widely used UC mouse model, the dextran sodium sulfate (DSS) model. We used this data in conjunction with publicly available human UC transcriptome data to compare gene expression profiles and pathways.RESULTSWe identified differentially regulated protein-coding genes, long non-coding RNAs and microRNAs from colon and blood of UC mice and further characterized the involved pathways and biological processes through which these genes may contribute to disease development and progression. By integrating human and mouse UC datasets, we suggest a set of 51 differentially regulated genes in UC colon and blood that may improve molecular phenotyping, aid in treatment decisions, drug discovery and the design of clinical trials.CONCLUSIONGlobal transcriptome analysis of the DSS-UC mouse model supports its use as an efficient high-throughput tool to discover new targets for therapeutic and diagnostic applications in human UC through identifying relationships between gene expression and disease phenotype.

scholarly journals Six host-range restricted poxviruses from three genera induce distinct gene expression profiles in an in vivo mouse model

BMC Genomics ◽  
2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Kristy Offerman ◽  
Armin Deffur ◽  
Olivia Carulei ◽  
Robert Wilkinson ◽  
Nicola Douglass ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Host Range ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Distinct Gene

scholarly journals Transcriptome analysis of gravitational effects on mouse skeletal muscles under microgravity and artificial 1 g onboard environment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Risa Okada ◽  
Shin-ichiro Fujita ◽  
Riku Suzuki ◽  
Takuto Hayashi ◽  
Hirona Tsubouchi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Transcriptome Analysis ◽  
Fiber Type ◽  
Expression Profiles ◽  
Space Station ◽  
Gene Expression Profiles

AbstractSpaceflight causes a decrease in skeletal muscle mass and strength. We set two murine experimental groups in orbit for 35 days aboard the International Space Station, under artificial earth-gravity (artificial 1 g; AG) and microgravity (μg; MG), to investigate whether artificial 1 g exposure prevents muscle atrophy at the molecular level. Our main findings indicated that AG onboard environment prevented changes under microgravity in soleus muscle not only in muscle mass and fiber type composition but also in the alteration of gene expression profiles. In particular, transcriptome analysis suggested that AG condition could prevent the alterations of some atrophy-related genes. We further screened novel candidate genes to reveal the muscle atrophy mechanism from these gene expression profiles. We suggest the potential role of Cacng1 in the atrophy of myotubes using in vitro and in vivo gene transductions. This critical project may accelerate the elucidation of muscle atrophy mechanisms.

scholarly journals P02.10 FocuSCOPE: a single cell, multi-omics solution to simultaneously analyze tumor variants and microenvironment

2021 ◽  
Vol 9 (Suppl 1) ◽  
pp. A12.1-A12
Author(s):  
Y Arjmand Abbassi ◽  
N Fang ◽  
W Zhu ◽  
Y Zhou ◽  
Y Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Microenvironment ◽  
Single Cell ◽  
High Throughput ◽  
Immune Cells ◽  
Genetic Variants ◽  
Expression Profiles ◽  
Single Cells ◽  
Gene Expression Profiles ◽  
Single Cell Sequencing

Recent advances of high-throughput single cell sequencing technologies have greatly improved our understanding of the complex biological systems. Heterogeneous samples such as tumor tissues commonly harbor cancer cell-specific genetic variants and gene expression profiles, both of which have been shown to be related to the mechanisms of disease development, progression, and responses to treatment. Furthermore, stromal and immune cells within tumor microenvironment interact with cancer cells to play important roles in tumor responses to systematic therapy such as immunotherapy or cell therapy. However, most current high-throughput single cell sequencing methods detect only gene expression levels or epigenetics events such as chromatin conformation. The information on important genetic variants including mutation or fusion is not captured. To better understand the mechanisms of tumor responses to systematic therapy, it is essential to decipher the connection between genotype and gene expression patterns of both tumor cells and cells in the tumor microenvironment. We developed FocuSCOPE, a high-throughput multi-omics sequencing solution that can detect both genetic variants and transcriptome from same single cells. FocuSCOPE has been used to successfully perform single cell analysis of both gene expression profiles and point mutations, fusion genes, or intracellular viral sequences from thousands of cells simultaneously, delivering comprehensive insights of tumor and immune cells in tumor microenvironment at single cell resolution.Disclosure InformationY. Arjmand Abbassi: None. N. Fang: None. W. Zhu: None. Y. Zhou: None. Y. Chen: None. U. Deutsch: None.

Abstract 268: Strain-specific Cardiac Fibroblast Response to Isoproterenol-induced Cardiac Fibrosis

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Shuin Park ◽  
Sara Ranjbarvaziri ◽  
Fides Lay ◽  
Peng Zhao ◽  
Aldons J Lusis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Expression Profiles ◽  
Inbred Mouse ◽  
Gene Expression Profiles ◽  
Mouse Strains ◽  
Sequencing Analysis ◽  
Different Strains

Fibroblasts are a heterogeneous population of cells that function within the injury response mechanisms across various tissues. Despite their importance in pathophysiology, the effects of different genetic backgrounds on fibroblast contribution to the development of disease has yet to be addressed. It has previously been shown that mice in the Hybrid Mouse Diversity Panel, which consists of 110 inbred mouse strains, display a spectrum in severity of cardiac fibrosis in response to chronic treatment of isoproterenol (ISO). Here, we characterized cardiac fibroblasts (CFbs) from three different mouse strains (C57BL/6J, C3H/HeJ, and KK/HIJ) which exhibited varying degrees of fibrosis after ISO treatment. The select strains of mice underwent sham or ISO treatment via intraperitoneally-implanted osmotic pumps for 21 days. Masson’s Trichrome staining showed significant differences in fibrosis in response to ISO, with KK/HIJ mice demonstrating the highest levels, C3H/HeJ exhibiting milder levels, and C57BL/6J demonstrating little to no fibrosis. When CFbs were isolated and cultured from each strain, the cells demonstrated similar traits at the basal level but responded to ISO stimuli in a strain-specific manner. Likewise, CFbs demonstrated differential behavior and gene expression in vivo in response to ISO. ISO treatment caused CFbs to proliferate similarly across all strains, however, immunofluorescence staining showed differential levels of CFb activation. Additionally, RNA-sequencing analysis revealed unique gene expression profiles of all three strains upon ISO treatment. Our study depicts the phenotypic heterogeneity of CFbs across different strains of mice and our results suggest that ISO-induced cardiac fibrosis is a complex process that is independent of fibroblast proliferation and is mainly driven by the activation/inhibition of genes involved in pro-fibrotic pathways.

scholarly journals Microbial single-cell RNA sequencing by split-pool barcoding

Science ◽  
2020 ◽  
Vol 371 (6531) ◽  
pp. eaba5257 ◽  
Author(s):  
Anna Kuchina ◽  
Leandra M. Brettner ◽  
Luana Paleologu ◽  
Charles M. Roco ◽  
Alexander B. Rosenberg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Rna Sequencing ◽  
High Throughput ◽  
Single Cell Analysis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Growth Stages ◽  
High Throughput Analysis ◽  
Single Cell Rna Sequencing

Single-cell RNA sequencing (scRNA-seq) has become an essential tool for characterizing gene expression in eukaryotes, but current methods are incompatible with bacteria. Here, we introduce microSPLiT (microbial split-pool ligation transcriptomics), a high-throughput scRNA-seq method for Gram-negative and Gram-positive bacteria that can resolve heterogeneous transcriptional states. We applied microSPLiT to >25,000 Bacillus subtilis cells sampled at different growth stages, creating an atlas of changes in metabolism and lifestyle. We retrieved detailed gene expression profiles associated with known, but rare, states such as competence and prophage induction and also identified unexpected gene expression states, including the heterogeneous activation of a niche metabolic pathway in a subpopulation of cells. MicroSPLiT paves the way to high-throughput analysis of gene expression in bacterial communities that are otherwise not amenable to single-cell analysis, such as natural microbiota.

Comparison of hepatocarcinogen-induced gene expression profiles in conventional primary rat hepatocytes with in vivo rat liver

2012 ◽  
Vol 86 (9) ◽  
pp. 1399-1411 ◽  
Author(s):  
Tatyana Y. Doktorova ◽  
Heidrun Ellinger-Ziegelbauer ◽  
Mathieu Vinken ◽  
Tamara Vanhaecke ◽  
Joost van Delft ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rat Liver ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Rat Hepatocytes ◽  
Primary Rat Hepatocytes

scholarly journals In Vivo mRNA Profiling of Uropathogenic Escherichia coli from Diverse Phylogroups Reveals Common and Group-Specific Gene Expression Profiles

mBio ◽  
2014 ◽  
Vol 5 (4) ◽  
Author(s):  
Piotr Bielecki ◽  
Uthayakumar Muthukumarasamy ◽  
Denitsa Eckweiler ◽  
Agata Bielecka ◽  
Sarah Pohl ◽  
...  
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Specific Gene ◽  
Content Type ◽  
E Coli ◽  
Human Host ◽  
Tract Infections

ABSTRACTmRNA profiling of pathogens during the course of human infections gives detailed information on the expression levels of relevant genes that drive pathogenicity and adaptation and at the same time allows for the delineation of phylogenetic relatedness of pathogens that cause specific diseases. In this study, we used mRNA sequencing to acquire information on the expression ofEscherichia colipathogenicity genes during urinary tract infections (UTI) in humans and to assign the UTI-associatedE. coliisolates to different phylogenetic groups. Whereas thein vivogene expression profiles of the majority of genes were conserved among 21E. colistrains in the urine of elderly patients suffering from an acute UTI, the specific gene expression profiles of the flexible genomes was diverse and reflected phylogenetic relationships. Furthermore, genes transcribedin vivorelative to laboratory media included well-described virulence factors, small regulatory RNAs, as well as genes not previously linked to bacterial virulence. Knowledge on relevant transcriptional responses that drive pathogenicity and adaptation of isolates to the human host might lead to the introduction of a virulence typing strategy into clinical microbiology, potentially facilitating management and prevention of the disease.IMPORTANCEUrinary tract infections (UTI) are very common; at least half of all women experience UTI, most of which are caused by pathogenicEscherichia colistrains. In this study, we applied massive parallel cDNA sequencing (RNA-seq) to provide unbiased, deep, and accurate insight into the nature and the dimension of the uropathogenicE. coligene expression profile during an acute UTI within the human host. This work was undertaken to identify key players in physiological adaptation processes and, hence, potential targets for new infection prevention and therapy interventions specifically aimed at sabotaging bacterial adaptation to the human host.

scholarly journals Distinct biological events generated by ECM proteolysis by two homologous collagenases

2016 ◽  
Vol 113 (39) ◽  
pp. 10884-10889 ◽  
Author(s):  
Inna Solomonov ◽  
Eldar Zehorai ◽  
Dalit Talmi-Frank ◽  
Sharon G. Wolf ◽  
Alla Shainskaya ◽  
...  
Keyword(s):  
Gene Expression ◽  
Viscoelastic Properties ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cell Behavior ◽  
Matrix Remodeling ◽  
Biochemical Process ◽  
Fundamental Understanding ◽  
Cell Crosstalk

It is well established that the expression profiles of multiple and possibly redundant matrix-remodeling proteases (e.g., collagenases) differ strongly in health, disease, and development. Although enzymatic redundancy might be inferred from their close similarity in structure, their in vivo activity can lead to extremely diverse tissue-remodeling outcomes. We observed that proteolysis of collagen-rich natural extracellular matrix (ECM), performed uniquely by individual homologous proteases, leads to distinct events that eventually affect overall ECM morphology, viscoelastic properties, and molecular composition. We revealed striking differences in the motility and signaling patterns, morphology, and gene-expression profiles of cells interacting with natural collagen-rich ECM degraded by different collagenases. Thus, in contrast to previous notions, matrix-remodeling systems are not redundant and give rise to precise ECM–cell crosstalk. Because ECM proteolysis is an abundant biochemical process that is critical for tissue homoeostasis, these results improve our fundamental understanding its complexity and its impact on cell behavior.

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