Gene expression variation upon folate deficiency and repletion in human foreskin keratinocytes immortalized by HPV16E6E7 Overall design: Effects of folate modulation on several cellular events such as DNA stability
Folate Repletion after Deficiency Induces Irreversible Genomic and Transcriptional Changes in Human Papillomavirus Type 16 (HPV16)-Immortalized Human Keratinocytes.
Specimen part, Subject
View SamplesPurpose: to identify the effects on the transcriptome of deleting ZFP36L1 in MZ B cells Overall design: Method (MZ B cells): RNAseq libraries were prepared from 5ng RNA isolated from sorted ex-vivo MZ B cells. Total RNA samples were sent to Aros Applied Biotechnology A/S and were prepared using the Clontech SMARTer kit. Libraries were sequenced (100bp paired end) on the Illumina Hiseq. Method (FO B cells): RNAseq libraries were prepared from RNA isolated from sorted ex-vivo FO B cells. Total RNA samples were sent to Aros Applied Biotechnology A/S and were prepared using the TruSeq Stranded mRNA Sample Prep Kit (Illumina). Libraries were sequenced (100bp single end) on the Illumina Hiseq.
Maintenance of the marginal-zone B cell compartment specifically requires the RNA-binding protein ZFP36L1.
Specimen part, Cell line, Subject
View SamplesThe current study was designed to investigate the actions of Anti-Mllerian Hormone (AMH) on primordial follicle assembly. Ovarian primordial follicles develop from the breakdown of oocyte nests during fetal development for the human and immediately after birth in rodents. AMH was found to inhibit primordial follicle assembly, decrease the initial primordial follicle pool size and promote the persistence of small oocyte nests in a rat ovarian organ culture. The AMH expression was found to be primarily in the stromal tissue of the ovaries at this period of development, suggesting a stromal-epithelial cell interaction for primordial follicle assembly. AMH was found to promote alterations in the ovarian transcriptome during primordial follicle assembly with over 200 genes with altered expression. A gene network was identified suggesting a potential central role for the Fgf2/Nudt6 antisense transcript in the follicle assembly process. A number of signal transduction pathways are regulated by AMH actions on the ovarian transcriptome, in particular the transforming growth factor beta (TGF) signaling process. AMH is the first hormone/protein shown to have an inhibitory action on primordial follicle assembly. Due to the critical role of the primordial follicle pool size for female reproduction, elucidation of the factors, such as AMH, that regulate the assembly process will provide insights into potential therapeutics to manipulate the pool size and female reproduction.
Inhibitory actions of Anti-Müllerian Hormone (AMH) on ovarian primordial follicle assembly.
Sex, Specimen part
View SamplesPurpose: Conditional knockout of Zfp36l1 Zfp36l2 in pro-B cells perturbs B cell development leading to reduced V(D)J recombination and diminished numbers of cells in successive stages of development. This RNA seq experiment aimed to determine the molecular pathways affected by loss of Zfp36l1 and Zfp36l2, and to deduce direct targets of these RNA binding proteins. Methods: RNAseq libraries were prepared from 0.1 µg of RNA from sorted control and DCKO late pre-B cells using TruSeq RNA sample preparation kit v2 modified to be strand specific using the dUTP method. Libraries were sequenced by an Illumina genome analyzer II measuring 54bp single-end reads. Over 30 million reads were measured from each sample. The reads were trimmed to remove adapter sequences using Trim Galore then mapped using Tophat (version 1.1.4) to the NCBIm37 mouse assembly (April 2007, strain C57BL/6J); reads with an identical sequence to more than one genomic locus were not mapped. Quality control analysis was carried out with FastQC. Results: Read counts for each gene were generated in SeqMonk: transcripts from the same gene were collapsed into a single transcript containing all exons, so total reads were counted without considering alternative splice forms. Since the libraries were strand-specific only reads on the opposing strand were counted. Differences in the abundance of transcripts between DCKO and control late pre-B cells were calculated in the R/Bioconductor program DESeq (version 1.12.1). Adjusted P values for differential expression were calculated in DESeq using a Benjamini-Hochberg correction: genes with an adjusted p-value of less than 5% were considered significant. Differentially expressed mouse transcripts identified using DESeq were analyzed for gene set enrichment using Toppfun. Conclusions: We identified an enrichment of mRNAs involved in cell cycle progression within Zfp36l1 Zfp36l2 double conditional knockouts. Overall design: RNAseq of late pre-B cells from control and Zfp36l1, Zfp36l2 double conditional knockout mice.
RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence.
Specimen part, Subject
View SamplesSexual selection involves mate preference behavior and is a critical determinant for natural selection and evolutionary biology. Previously an environmental compound (fungicide vinclozolin) was found to promote epigenetic transgenerational inheritance of modified mate selection characteristics in all progeny for three generations after exposure of a gestating female. The current study investigated gene networks involved in various regions of the brain that correlated with the mate preference behavior altered in F3-Vinclozolin lineage animals. Statistically significant correlations of differentially expressed gene clusters and modules were identified to associate with specific mate preference behaviors. This novel systems biology approach identified critical gene networks involved in mate preference behavior and demonstrated the ability of environmental factors to promote epigenetic transgenerational inheritance of this altered evolutionary biology determinant. Combined observations elucidate the potential molecular control of mate preference behavior and suggests environmental epigenetics can have a role in evolutionary biology.
Gene bionetworks involved in the epigenetic transgenerational inheritance of altered mate preference: environmental epigenetics and evolutionary biology.
Sex, Age, Specimen part
View SamplesEnvironmentally induced epigenetic transgenerational inheritance of adult onset disease involves a variety of phenotypic changes suggesting a general alteration in genome activity. Investigation of eleven different tissue transcriptomes in male and female F3 generation vinclozolin versus control lineage rats demonstrated all tissues examined had unique transgenerational transcriptomes. Common cellular pathways and processes were identified among the tissues. A bionetwork analysis identified gene modules with coordinated gene expression and each had unique gene networks regulating tissue specific gene expression and function. A large number of statistically significant over-represented clusters of differentially expressed genes were identified and termed Epigenetic Control Regions. Combined observations demonstrate that all tissues derived from the epigenetically altered germ line develop transgenerational transcriptomes unique to the tissue, but common epigenetic control regions in the genome appear to in part coordinately regulate these tissue specific transcriptomes. This systems biology approach provides insight into the molecular mechanisms involved in the epigenetic transgenerational inheritance of a variety of adult onset disease phenotypes.
Epigenetic transgenerational inheritance of somatic transcriptomes and epigenetic control regions.
Sex, Specimen part
View SamplesEmbryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination promotes an epigenetic reprogramming of the male germ-line that is associated with transgenerational adult onset disease states. Further analysis of this transgenerational phenotype on the brain demonstrated reproducible changes in the brain transcriptome three generations (F3) removed from the exposure. The transgenerational alterations in the male and female brain transcriptomes were distinct. In the males, the expression of 92 genes in the hippocampus and 276 genes in the amygdala were transgenerationally altered. In the females, the expression of 1,301 genes in the hippocampus and 172 genes in the amygdala were transgenerationally altered. Analysis of specific gene sets demonstrated that several brain signaling pathways were influenced including those involved in axon guidance and long-term potentiation. An investigation of behavior demonstrated that the vinclozolin F3 generation males had a decrease in anxiety-like behavior, while the females had an increase in anxiety-like behavior. These observations demonstrate that an embryonic exposure to an environmental compound appears to promote a reprogramming of brain development that correlates with transgenerational sex-specific alterations in the brain transcriptomes and behavior. Observations are discussed in regards to environmental and transgenerational influences on the etiology of brain disease.
Transgenerational epigenetic programming of the brain transcriptome and anxiety behavior.
No sample metadata fields
View SamplesThe current study investigates the direct effects of in utero vinclozolin exposure on the developing rat testis transcriptome. Vinclozolin is a commonly used fungicide in agriculture and is an endocrine disruptor with anti-androgenic activity. Previous studies have demonstrated that exposure to vinclozolin during embryonic gonadal sex determination induces epigenetic modifications of the germ line and transgenerational adult onset disease states that include spermatogenic cell defects, prostate disease, kidney disease, and tumor development. An investigation of the molecular actions of vinclozolin was initiated through an analysis of direct actions on the F1 generation embryonic testis development. Microarray analyses were performed to compare control and vinclozolin treated testis transcriptomes at embryonic day 13, 14 and 16. A total of 576 differentially expressed genes were identified and the major cellular functions and pathways associated with these altered transcripts were examined. The sets of regulated genes at the different development periods were found to be transiently altered and distinct. Interestingly, genes previously shown to be regulated during normal male sex determination were not altered by vinclozolin treatment. Categorization by major known functions of all 576 genes altered by in utero vinclozolin exposure demonstrates transcription, signaling, cytoskeletal and extra cellular matrix associated transcripts are highly represented. Specific cellular process and pathway analyses suggest the involvement of Wnt and calcium signaling, vascular development and epigenetic mechanisms as potential mediators of the direct F1 generation actions of vinclozolin.
Alterations in the developing testis transcriptome following embryonic vinclozolin exposure.
Sex, Specimen part
View SamplesCoordinated interactions between ovarian granulosa and theca cells are required for female endocrine function and fertility. To elucidate these interactions the regulation of the granulosa and theca cell transcriptomes during bovine antral follicle development were investigated. Granulosa cells and theca cells were isolated from small (<5 mm), medium (5-10 mm), and large (>10 mm) antral bovine follicles. A microarray analysis of 24,000 bovine genes revealed that granulosa cells and theca cells each had gene sets specific to small, medium and large follicle cells. Transcripts regulated (i.e., minimally changed 1.5-fold) during antral follicle development for the granulosa cells involved 446 genes and for theca cells 248 genes. Only 28 regulated genes were common to both granulosa and theca cells. Regulated genes were functionally categorized with a focus on growth factors and cytokines expressed and regulated by the two cell types. Candidate regulatory growth factor proteins mediating both paracrine and autocrine cell-cell interactions include macrophage inflammatory protein (MIP1 beta), teratocarcinoma-derived growth factor 1 (TDGF1), stromal derived growth factor 1 (SDF1; i.e., CXCL12), growth differentiation factor 8 (GDF8), glia maturation factor gamma (GMFG), osteopontin (SPP1), angiopoietin 4 (ANGPT4), and chemokine ligands (CCL 2, 3, 5, and 8). The current study examined granulosa cell and theca cell regulated genes associated with bovine antral follicle development and identified candidate growth factors potentially involved in the regulation of cell-cell interactions required for ovarian function.
Regulation of granulosa and theca cell transcriptomes during ovarian antral follicle development.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Environmentally induced epigenetic transgenerational inheritance of altered Sertoli cell transcriptome and epigenome: molecular etiology of male infertility.
Sex, Age, Specimen part, Treatment
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