Comparative transcriptomic analysis reveals translationally relevant processes in mouse models of malaria.
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ABSTRACT:
SUBMITTER: Georgiadou A
PROVIDER: S-EPMC8747512 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We performed Dual (host and pathogen) RNA-sequencing on whole blood of C57BL/6 mice infected with Plasmodium berghei ANKA, Plasmodium berghei NK65, Plasmodium yoelii 17XL, Plasmodium yoelii 17XNL, or Plasmodium chabaudi AS at their respective early and late stage of infection.
| PRJEB43641 | ENA
Project description:Stress often affects eating behaviors, leading to increased eating in some individuals and decreased eating in others. Identifying physiological and psychological factors that determine the direction of eating responses to stress has been a major goal of epidemiological and clinical studies. However, challenges of standardizing the stress exposure in humans hinder efforts to uncover the underlying mechanisms. The issue of what determines the direction of stress-induced feeding responses has not been directly addressed in animal models, but assays that combine stress with a feeding-related task are commonly used as readouts of other behaviors, such as anxiety. Sex, estrous cyclicity, circadian cyclicity, caloric restriction, palatable diets, elevated body weight, and properties of the stressors similarly influence feeding behavior in humans and rodent models. Yet, most rodent studies do not use conditions that are most relevant for studying feeding behavior in humans. This review proposes a conceptual framework for incorporating these influences to develop reproducible and translationally relevant assays to study effects of stress on food intake. Such paradigms have the potential to uncover links between emotional eating and obesity as well as to the etiology of eating disorders.
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Project description:Mouse models of non-alcoholic fatty liver disease (NAFLD) are required to define therapeutic targets, but detailed time-resolved studies to establish a sequence of events are lacking. Here, we fed male C57Bl/6N mice a Western or standard diet over 48 weeks. Multiscale time-resolved characterization was performed using RNA-seq, histopathology, immunohistochemistry, intravital imaging, and blood chemistry; the results were compared to human disease. Acetaminophen toxicity and ammonia metabolism were additionally analyzed as functional readouts. We identified a sequence of eight key events: formation of lipid droplets; inflammatory foci; lipogranulomas; zonal reorganization; cell death and replacement proliferation; ductular reaction; fibrogenesis; and hepatocellular cancer. Functional changes included resistance to acetaminophen and altered nitrogen metabolism. The transcriptomic landscape was characterized by two large clusters of monotonously increasing or decreasing genes, and a smaller number of 'rest-and-jump genes' that initially remained unaltered but became differentially expressed only at week 12 or later. Approximately 30% of the genes altered in human NAFLD are also altered in the present mouse model and an increasing overlap with genes altered in human HCC occurred at weeks 30-48. In conclusion, the observed sequence of events recapitulates many features of human disease and offers a basis for the identification of therapeutic targets.
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Project description:BackgroundThe liver is responsible for a range of functions in vertebrates, such as metabolism and immunity. In malaria, the liver plays a crucial role in the interaction between the parasite and host. Although malarial hepatitis is a common clinical complication of severe malaria, other malaria-related liver changes have been overlooked during the blood stage of the parasite life-cycle, in contrast to the many studies that have focused on parasite invasion of and replication in the liver during the hepatic stage of the parasite.MethodsA rodent model of malaria was established using Plasmodium yoelii strain 17XL, a lethal strain of rodent malaria, for liver transcriptomic profiling.ResultsDifferentially expressed messenger RNAs were associated with innate and adaptive immune responses, while differentially expressed long noncoding RNAs were enriched in the regulation of metabolism-related pathways, such as lipid metabolism. The coexpression network showed that host genes were related to cellular transport and tissue remodeling. Hub gene analysis of P. yoelii indicated that ubiquitination genes that were coexpressed with the host were evolutionarily conserved.ConclusionsOur analysis yielded evidence of activated immune responses, aberrant metabolic processes and tissue remodeling changes in the livers of mice with malaria during the blood stage of the parasite, which provided a systematic outline of liver responses during Plasmodium infection.
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Project description:BackgroundPersimmon (Diospyros kaki) is the most economically cultivated species belonging to the genus Diospyros. However, little is known about the interspecific diversity and mechanism of domestication, partly due to the lack of genomic information that is available for closely related species of D. kaki (DK). Here, we performed transcriptome sequencing on nine samples, including DK, a variety of DK and seven closely related species, to evaluate the interspecific genetic divergence and to identify candidate genes involved in persimmon domestication.ResultsWe obtained a total of 483,421 unigenes with N50 at 1490 bp in the nine Diospyros samples and identified 2603 orthogroups that were shared among all the samples using OrthoMCL analysis. A phylogenetic tree was established based on the tandem 2603 one-to-one single copy gene alignments, showing that DK was closely related to D. kaki var. silvestris (DKV) and that it clustered with the clade of D. deyangnsis (DD) and was farthest from the D. cathayensis (DC) species. The nonsynonymous substitutions (Ka), via synonymous substitution (Ks) ratios, was directly proportional to the genetic relationship of the different species. The higher the Ka/Ks ratios, the longer the distance was. Moreover, 31 positively selected genes (PSGs) involved in carbohydrate metabolism and phenolic metabolism were identified and isolated, and nearly all PSGs except the MATE gene had a high expression in the DK or DKV species. It was hypothesized that these genes might contribute to the domestication of the DK species. Finally, we developed the expressed sequence tag-simple sequence repeat (EST-SSR) and identified 2 unique amplicons DKSSR10 and DKSSR39: the former was absent in the DC species but was present in the other species, the latter had a long amplification product in the DJ species.ConclusionThis study presents the first transcriptome resources for the closely related species of persimmon and reveals interspecific genetic divergence. It is speculated that DK is derived from the hybridization of DD and DO species. Furthermore, our analysis suggests candidate PSGs that may be crucial for the adaptation, domestication, and speciation of persimmon relatives and suggests that DKSSR10 and DKSSSR39 could potentially serve as species-specific molecular markers.
| S-EPMC6543618 | biostudies-literature
Project description:Cyanobacteria are photosynthetic organisms and are the only prokaryotes known to have a circadian lifestyle. Unicellular diazotrophic cyanobacteria such as Cyanothece sp. ATCC 51142 produce oxygen and can also fix atmospheric nitrogen, a process exquisitely sensitive to oxygen. To accommodate such antagonistic processes, the intracellular environment of Cyanothece oscillates between aerobic and anaerobic conditions during a day-night cycle. This is accomplished by temporal separation of the two processes: photosynthesis during the day and nitrogen fixation at night. Although previous studies have examined periodic changes in transcript levels for a limited number of genes in Cyanothece and other unicellular diazotrophic cyanobacteria, a comprehensive study of transcriptional activity in a nitrogen-fixing cyanobacterium is necessary to understand the impact of the temporal separation of photosynthesis and nitrogen fixation on global gene regulation and cellular metabolism. We have examined the expression patterns of nearly 5,000 genes in Cyanothece 51142 during two consecutive diurnal periods. Our analysis showed that approximately 30% of these genes exhibited robust oscillating expression profiles. Interestingly, this set included genes for almost all central metabolic processes in Cyanothece 51142. A transcriptional network of all genes with significantly oscillating transcript levels revealed that the majority of genes encoding enzymes in numerous individual biochemical pathways, such as glycolysis, oxidative pentose phosphate pathway, and glycogen metabolism, were coregulated and maximally expressed at distinct phases during the diurnal cycle. These studies provide a comprehensive picture of how a physiologically relevant diurnal light-dark cycle influences the metabolism in a photosynthetic bacterium.
| S-EPMC2329701 | biostudies-literature
Project description:<p>Malaria varies in severity, with complications ranging from uncomplicated to severe malaria. Severe malaria could be attributed to peripheral hyperparasitemia or cerebral malaria. The metabolic interactions between the host and <em>Plasmodium</em> species are yet to be understood during these infections of varied pathology and severity. An untargeted metabolomics approach utilizing the liquid chromatography-mass spectrometry platform has been used to identify the affected host metabolic pathways and associated metabolites in the serum of murine malaria models with uncomplicated malaria, hyperparasitemia and experimental cerebral malaria. We report that mice with malaria share similar metabolic attributes like higher levels of bile acids, bile pigments, and steroid hormones that have been reported for human malaria infections. Moreover, in severe malaria, upregulated levels of metabolites like phenylalanine, histidine, valine, pipecolate, ornithine and pantothenate, with decreased levels of arginine and hippurate, were observed. Metabolites of sphingolipid metabolism were upregulated in experimental cerebral malaria. Higher levels of 20-hydroxy-leukotriene B4 and epoxyoctadecamonoenoic acids were found in uncomplicated malaria, with lower levels observed for experimental cerebral malaria. Our study provides insights into host biology during different pathological stages of malaria disease and would be useful for the selection of animal models for evaluating diagnostic and therapeutic interventions against malaria.</p>
2022-09-14 | MTBLS4387 | MetaboLights
Project description:The mouse is widely used to study decidualization and there are three well-established mouse models of decidualization, namely natural pregnancy decidualization (NPD), artificial decidualization (AD), and in vitro decidualization (IVD). However, the extent of similarity and difference between these models at the molecular level remains largely unknown. Here, we performed a comparative analysis using the RNA-seq approach. In the NPD model, which is thought to be the golden standard of mouse decidualization, we found a total of 5277 differentially expressed genes, with 3158 genes being up-regulated and 2119 genes being down-regulated. A total of 4294 differentially expressed genes were identified in the AD model: 1127 up-regulated genes and 3167 down-regulated genes. In comparison to NPD, 1977 genes were consistently expressed, whereas only 217 genes were inconsistently expressed, indicating that AD is a reliable model for mouse decidualization. In the IVD model, RNA-seq analysis revealed that 513 genes were up-regulated and 988 genes were down-regulated. Compared to NPD, 310 genes were consistently expressed, whereas 456 genes were inconsistently expressed. Moreover, although the decidualization marker Prl8a2 (prolactin family 8 subfamily a member 2) was up-regulated, the widely-used marker Alpl (alkaline phosphatase liver/bone/kidney) was down-regulated in the IVD model. Therefore, we suggest that the IVD model should be optimized to mimic NPD at the transcriptomic level. Our study contributes to an increase in the knowledge about mouse models of decidualization.
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Project description:Pectoralis phenotypic variation plays a fundamental role in locomotion and thermogenesis in highland birds. However, its regulatory and metabolic mechanisms remain enigmatic to date. Here, we integrated phenomic, transcriptomic, and metabolomic approaches to determine muscle variation and its underpinning mechanisms across altitudinal songbirds. Phenomics confirmed that all highland birds had considerable increases in muscle oxidative capacity, capillarity, and mitochondrial abundance in our study. Correspondingly, transcriptomic analyses found that differentially expressed genes in phenotype-associated modules enriched for blood vessel, muscle structure development, and mitochondrial organization. Despite similar traits and functional enrichments across highland birds, different mechanisms drove their occurrence in high-altitude tree sparrow and 2 snow finches. Importantly, a metabolic feature shared by all the 3 highland birds is the improvement in insulin sensitivity and glucose utilization through activating insulin signaling pathway, which is vital to increase muscle oxidative capacity and maintain metabolic homeostasis. Nevertheless, fatty acid biosynthesis and oxidation are enhanced in only 2 snow finches which had a long evolutionary history on the high plateau, also differing from ketone body metabolism in recently introduced colonizer of the tree sparrow of the high plateau. Our study represents a vital contribution to reveal the regulatory and metabolic basis of pectoralis variation across altitudinal songbirds.
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Project description:PurposeThe purpose of this study was to identify key genes and their regulatory networks that are conserved in mouse models of age-related macular degeneration (AMD) and human AMD.MethodsRetinal RNA-Seq was performed in laser-induced choroidal neovascularization (CNV) mice at day 3 and day 7 after photocoagulation. Mass spectrometry-based proteomic analysis was performed with retinas collected at day 3. Retinal RNA-Seq data was further compared among mouse models of laser-induced CNV and NaIO3-induced retinal degeneration (RD) and a large AMD cohort.ResultsRetinal RNA-Seq revealed upregulated genes and pathways related to innate immunity and inflammation in mice with CNV, with more profound changes at the early stage (day 3). Proteomic analysis further validated these differentially expressed genes and their networks in retinal inflammation during CNV. Notably, the most evident overlap in the retina of mice with laser-induced CNV and NaIO3-induced RD was the upregulation of inflammation-related genes, pointing to a common vital role of retinal inflammation in the early stage for both mouse AMD models. Further comparative transcriptomic analysis of the mouse AMD models and human AMD identified 48 conserved genes mainly involved in inflammation response. Among them, B2M, C3, and SERPING1 were upregulated in all stages of human AMD and the mouse AMD models compared to controls.ConclusionsOur study demonstrates conserved molecular changes related to retinal inflammation in mouse AMD models and human AMD and provides new insight into the translational application of these mouse models in studying AMD mechanisms and treatments.
| S-EPMC10774692 | biostudies-literature