RNA-Seq of Nothobranchius furzeri brain of male and female with an age of 39-108 days post hatch (dph).
Ontology highlight
ABSTRACT: A vast body of studies is available that describes age-dependent gene expression in relationship to aging in a number of different model species. These data were obtained from animals kept in conditions with reduced environmental challenges, abundant food and deprivation of natural sensory stimulation. Here we compared wild- and captive-aging in the short-lived turquoise killifish (Nothobranchius furzeri). These fish inhabit temporary ponds in the African savannah and when the ponds are flooded eggs hatch synchronously enabling a precise timing of the population age. We collected brains for wild fish of different ages and quantified the global age-dependent regulation of transcripts using RNAseq. A major difference between captive and wild population is that wild population reach larger sizes and cease their growth rapidly, enabling the analysis of age-dependent gene expression without the confounding effect of adult brain growth.We found that the majority of differentially-expressed genes show the same direction of regulation in wild- and captive-population. However, a number of genes were regulated in opposite direction. Genes down-regulated in the wild and up-regulated in captivity were enriched for terms related to neuronal communication. Genes up-regulated in the wild and down-regulated in captive conditions were up-regulated in terms related to DNA replication. Finally, the rate of age-dependent gene regulation was higher in the wild animals suggesting a phenomenon of accelerated aging.
Project description:A vast body of studies is available that describes age-dependent gene expression in relationship to aging in a number of different model species. These data were obtained from animals kept in conditions with reduced environmental challenges, abundant food and deprivation of natural sensory stimulation. Here we compared wild- and captive-aging in the short-lived turquoise killifish (Nothobranchius furzeri). These fish inhabit temporary ponds in the African savannah and when the ponds are flooded eggs hatch synchronously enabling a precise timing of the population age. We collected brains for wild fish of different ages and quantified the global age-dependent regulation of transcripts using RNAseq. A major difference between captive and wild population is that wild population reach larger sizes and cease their growth rapidly, enabling the analysis of age-dependent gene expression without the confounding effect of adult brain growth.We found that the majority of differentially-expressed genes show the same direction of regulation in wild- and captive-population. However, a number of genes were regulated in opposite direction. Genes down-regulated in the wild and up-regulated in captivity were enriched for terms related to neuronal communication. Genes up-regulated in the wild and down-regulated in captive conditions were up-regulated in terms related to DNA replication. Finally, the rate of age-dependent gene regulation was higher in the wild animals suggesting a phenomenon of accelerated aging.
Project description:Background: Aquaculture of the black tiger prawn Penaeus monodon remains severely constrained by an almost total dependence on wild-caught broodstock. Reliance on wild-caught broodstock stems, for the most part, from reduced reproductive potential of captive-reared females. Reproductive performance of captive-reared females is usually characterised by longer latency period, lower egg production, egg hatch rates and post-larval survivorship compared with their wild-caught counterparts. Improved understanding of the cellular and associated molecular events occurring during peneaid ovarian maturation could therefore be fundamental to improving reproductive success of captive-reared animals. Methodology/Principle Findings: In support of other studies, our histological analyses of developing oocytes revealed differences between wild-caught and captive-reared P. monodon, including reduced lipid accumulation in oocytes of captive-reared animals. We have employed oligonucleotide microarray analysis to compare expression profiles of genes involved in ovarian maturation among wild-caught and captive-reared animals. Custom oligonucleotide microarrays were constructed and screened with transcripts derived from the ovary, cephalothorax and eyestalk from animals of all ovarian maturation stages. Ovarian maturation-related differential expression patterns were observed for 111 transcripts, with 53 transcripts displaying differential expression between wild-caught and captive-reared animals. Notably transcripts encoding vitellogenin - the major egg yolk protein precursor, and a lipid storage droplet protein (which we named pmLSD) which is involved in lipid accumulation, were found to be more highly expressed in wild-caught animals. pmLSD transcripts localise to pre-vitellogenic oocytes of wild-caught animals and the pmLSD protein is exclusively localised to the surface of lipid droplets of oocytes at vitellogenic and cortical rod stages. We have employed oligonucleotide microarray analysis to compare expression profiles of genes involved in ovarian maturation among wild-caught and captive-reared animals. Target preparation and microarray hybridisation. Ovarian RNA samples from nine wild-caught animals representing six ovarian maturation stages (P, 2, 24, V, R, E) were used in microarray hybridisations. Similarly, RNA samples from three captive-reared animals representing four maturation stages (P, 24, V, E) were used in microarray hybridisations. For wild-caught animals, samples from each ovarian maturation stage were pooled into groups of four and five, enabling two hybridisations. For captive-reared animals, samples from each ovarian maturation stage from all three animals were pooled enabling one hybridisation for each stage. Importantly, as the four stages for captive-reared animals were (1) pre-ablation pre-vitellogenic, (2) post-ablation pre-vitellogenic, (3) post-ablation vitellogenic, (4) post-ablation vitellogenic with cortical rods, this arrangement allowed for 2 samples of captive-reared pre-vitellogenic and 2 samples of captive-reared vitellogenic, thereby enabling t-tests between samples, while also allowing analysis across the whole 4 stages via cluster analysis. All hybridisations were single channel hybridisations conducted using equal amounts of RNA pooled from each individual.
Project description:The black-footed ferret (Mustela nigripes) is a star example of the efforts of conservation programs in bringing endangered species back from the brink of extinction. As one of the world’s most endangered mammals, the vast majority of black-footed ferrets living in the wild today are the offspring of a founding captive population. The success of this ongoing breeding program, however, is threatened by inbreeding depression and the observed decline in pregnancy rates since its founding. As the wild and modern captive populations share a genetic history, the greatest difference between the two groups is the captive environment of the breeding program. In this study, we used RNA sequencing and proteomics for the first time in black-footed ferrets to explore whether the diet of wild ferrets versus captive diet variants could explain the differences in fertility and sperm characteristics observed between each population. We find that changes in both the transcriptional and proteomic profile of black-footed ferret ejaculate are strongly associated with differences in fertility, especially in pathways associated with innate immunity and metabolism; that transcriptional changes are further exacerbated by diet. Overall, our results support the hypothesis of ongoing environmental-dependent inbreeding depression in the black-footed ferret, with a need to re-evaluate dietary and environmental parameters of the conservation program; and also illustrates the value of multi-level genomics for conservation management programs.
Project description:An Infinium microarray platform (GPL28271, HorvathMammalMethylChip40) was used to generate DNA methylation data from many tissues of plains zebras (Equus quagga). Both whole blood (96) and remote biopsy (24) samples were obtained from a captive population of zebras maintained in a semi-wild state. After eliminating samples with low confidence for individual identity and age, we retained 76 blood samples and 20 biopsy samples, totaling 96 zebra samples.
Project description:Spotted seals (Phoca largha) is a critically endangered pinniped in China and South Korea. Captive in artificially controlled environment is a conventional method to protect and maintain the population of this species. However, little is known about the physiological differences between the wild and captive P. largha. In order to draw the preliminary protein expression profile in the P. largha, blood from the wild and captive pups were subjected to a label-free comparative proteomic analysis. According to the results, 972 proteins were identified, which performed functions related to various metabolic, immune and cellular processes. Among these identified proteins, the expression level of 51 proteins significantly changed between the wild and captive P. large pups. These differentially expressed proteins were enriched in a wide range of cellular functions, including cytoskeleton, phagocytosis. proteolysis, gene expression regulation and carbohydrate metabolism. The activities of phagocytosis and its related ubiquitin mediated proteolysis were significantly higher in the blood of wild P. largha pups than in captive individuals. In addition, a key protein associated with the differences in the wild and captive P. largha pups, heat shock protein 90-beta, were determined due to the most interactions of it with various differentially expressed proteins. Moreover, the wild P. largha pups could be more nutritionally stressed and have more powerful immune capacity. Our study provides the first data on the preliminary protein composition and gives useful information for the physiological characteristics research in this species.
Project description:The kidney is an excellent model for studying organ aging, but little is known about the molecular changes that take place during the aging process. In this article we measured mRNA expression and protein expression in a large cohort of Diversity Outbred mice at 6, 12, and 18 months of age, and studied the relationship between the changes we observe in mRNA and protein expression as a function of age. We observed enrichments of specific pathways including those that were previously observed to have significant changes with age at the mRNA level, and here we also identified enriched pathways at the protein level. Our analysis of the direction of change in mRNA and protein levels with age at the total population level revealed distinct functional groups that have either concordant or discordant changes in expression levels. The age-interactive quantitative trait loci (QTL) analysis of mRNA (eQTL) and protein (pQTL) revealed many distantly regulated loci as opposed to the many locally regulated eQTL and pQTL observed without age-interaction. From this, we found a locus on chromosome 12 and chromosome 15 to regulate many age-interactive eQTL and pQTL respectively. Overall, our findings demonstrate that the changes with age in the kidney at the protein level are distinctly different from the changes at the mRNA level and are not mediated by mRNA expression.
Project description:Hippocampal overexpression of FK506-binding protein 12.6/1b (FKBP1b), a negative regulator of ryanodine receptor Ca2+ release, reverses aging-induced memory impairment and neuronal Ca2+ dysregulation. Here, we test the hypothesis that FKBP1b also can protect downstream transcriptional networks from aging-induced dysregulation. We gave hippocampal microinjections of FKBP1b-expressing viral vector to male rats at either 13-months-of-age (long-term) or 19-months-of-age (short-term) and tested memory performance in the Morris water maze at 21-months-of-age. Aged rats treated short- or long-term with FKBP1b substantially outperformed age-matched vector controls and performed similarly to each other and young controls. Transcriptional profiling in the same animals identified 2342 genes whose hippocampal expression was up-/down-regulated in aged controls vs. young controls (the aging effect). Of these aging-dependent genes, 876 (37%) also showed altered expression in aged FKBP1b-treated rats compared to aged controls, with FKBP1b restoring expression of essentially all such genes (872/876, 99.5%) in the direction opposite the aging effect and closer to levels in young controls. This inverse relationship between the aging and FKBP1b effects suggests that the aging effects arise from FKBP1b deficiency. Functional category analysis revealed that genes downregulated with aging and restored by FKBP1b associated predominantly with diverse brain structure categories, including cytoskeleton, membrane channels and extracellular region. Conversely, genes upregulated with aging but not restored by FKBP1b associated primarily with glial-neuroinflammatory, ribosomal and lysosomal categories. Immunohistochemistry confirmed aging-induced rarefaction, and FKBP1b-mediated restoration, of neuronal microtubular structure. Thus, a previously-unrecognized genomic network modulating diverse brain structural processes is dysregulated by aging and restored by FKBP1b overexpression.
Project description:Background: Aquaculture of the black tiger prawn Penaeus monodon remains severely constrained by an almost total dependence on wild-caught broodstock. Reliance on wild-caught broodstock stems, for the most part, from reduced reproductive potential of captive-reared females. Reproductive performance of captive-reared females is usually characterised by longer latency period, lower egg production, egg hatch rates and post-larval survivorship compared with their wild-caught counterparts. Improved understanding of the cellular and associated molecular events occurring during peneaid ovarian maturation could therefore be fundamental to improving reproductive success of captive-reared animals. Methodology/Principle Findings: In support of other studies, our histological analyses of developing oocytes revealed differences between wild-caught and captive-reared P. monodon, including reduced lipid accumulation in oocytes of captive-reared animals. We have employed oligonucleotide microarray analysis to compare expression profiles of genes involved in ovarian maturation among wild-caught and captive-reared animals. Custom oligonucleotide microarrays were constructed and screened with transcripts derived from the ovary, cephalothorax and eyestalk from animals of all ovarian maturation stages. Ovarian maturation-related differential expression patterns were observed for 111 transcripts, with 53 transcripts displaying differential expression between wild-caught and captive-reared animals. Notably transcripts encoding vitellogenin - the major egg yolk protein precursor, and a lipid storage droplet protein (which we named pmLSD) which is involved in lipid accumulation, were found to be more highly expressed in wild-caught animals. pmLSD transcripts localise to pre-vitellogenic oocytes of wild-caught animals and the pmLSD protein is exclusively localised to the surface of lipid droplets of oocytes at vitellogenic and cortical rod stages.
Project description:Age is a key demographic in conservation biology where individual age classes show diffuse differences in terms of important population dynamics metrics such as morbidity and mortality. Furthermore, several traits including reproductive potential show clear senescence with aging. Thus, the ability to estimate the ages for the individuals of a population as part of age class assignment is critical in understanding both the current population structure as well as in modelling and predicting the future survival of species. This study explored the utility of age-related changes in methylation for six candidate genes, EDARADD, ELOVL2, FHL2, GRIA2, ITGA2B, and PENK, to create an age estimation model in captive cheetah. Gene orthologues between humans and cheetah were retrieved from NCBI containing a hundred CpG’s. Target regions were assayed for differential methylation and fragmentation patterns in fifty samples using mass array technology for a total of seventy-seven CpG clusters. Correlation analyses between CpG methylation and chronological age identified six CpG’s with an age relationship, of which four were hypomethylated and two were hypermethylated. Regression models, fitted for different combinations of CpG’s, indicated that age models using four and six CpG’s were most accurate, with the six CpG model having superior correlation and predictive power (R2 = 0.70, Mean Absolute Error = 25 months). This model was more accurate than previous attempts using methylation sensitive Polymerase Chain Reaction and performed similarly to models created using a candidate gene approach in several other mammal species, making methylation a promising tool of age estimation in cheetah.
Project description:A detailed knowledge of the mechanisms underlying brain aging is fundamental to understand its functional decline and the baseline upon which brain pathologies superimpose. Endogenous protective mechanisms must contribute to the adaptability and plasticity still present in the healthy aged brain. Apolipoprotein D (ApoD) is one of the few genes with a consistent and evolutionarily conserved up-regulation in the aged brain. ApoD protecting roles upon stress or injury are well known, but a study of the effects of ApoD expression in the normal aging process is still missing. Using an ApoD-knockout mouse we analyze the effects of ApoD on factors contributing to the functional maintenance of the aged brain. We focused our cellular and molecular analyses in cortex and hippocampus at an age representing the onset of senescence where mortality risks are below 25%, avoiding bias towards long-lived animals. Lack of ApoD causes a prematurely aged brain without altering lifespan. Age-dependent hyperkinesia and memory deficits are accompanied by differential molecular effects in cortex and hippocampus. Transcriptome analyses reveal distinct effects of ApoD loss on the molecular age-dependent patterns of cortex and hippocampus, with different cell-type contributions to age-regulated gene expression. Markers of glial reactivity, proteostasis, and oxidative and inflammatory damage reveal early signs of aging and enhanced brain deterioration in the ApoD-knockout brain. The lack of ApoD results in an age-enhanced significant reduction in neuronal calcium-dependent functionality markers and signs of early reduction of neuronal numbers in the cortex, thus impinging upon parameters clearly differentiating neurodegenerative conditions from healthy brain aging. Our data support the hypothesis that the physiological increased brain expression of ApoD represents a homeostatic anti-aging mechanism. The brain cortex and hippocampus of young and aged mice of wild-type and ApoD-KO genotypes were used for RNA extraction and hybridization on Affymetrix microarrays. We aim at identifying distinct effects of ApoD loss on the molecular age-dependent patterns of cortex and hippocampus.