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 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 SamplesThis dataset contains whole-genome RNA sequencing results from rat embryonic hippocampal neuronal cultures and serves as the basis for characterization of CRISPR/dCas9 gene activation in neuronal systems. Overall design: This experiment contains 9 biological samples, each of which underwent directional, paired-end PolyA+ RNA-seq on an Illumina Next-seq 500. Samples were treated with Lacz sgRNA (LZ2, LZ4, & LZ5), Bdnf-I sgRNA (B16, B17, B18), or Bdnf-IV sgRNA (BIV11, BIV14, BIV15), in addition to a dCas9-VPR fusion. Datasets were obtained using RNA-seq from PolyA+ fractions fractions of RNA. Each sample has multiple files, corresponding to different sequencing lanes (e.g., L001, L002, etc) or different reads (e.g., R1, R2).
A Neuron-Optimized CRISPR/dCas9 Activation System for Robust and Specific Gene Regulation.
Specimen part, Cell line, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Sex and strain dependent differences in mucosal immunology and microbiota composition in mice.
Sex, Specimen part
View SamplesA dysbiosis in the intestinal microbiome plays a role in the pathogenesis of several immunological diseases. These diseases often show a gender bias, suggesting gender differences in immune responses and in the intestinal microbiome. We hypothesized that gender differences in immune responses are associated with gender differences in microbiota. We demonstrated mouse strain dependent gender differences in the intestinal microbiome. Interestingly, a cluster of colonic genes (related to humoral and cell-mediated immune responses) correlated oppositely with microbiota species abundant in B6 females and in BALB/c males. This suggests that with different genetic backgrounds, gender associated immune responses are differentially regulated by microbiota. The net result was the same, since both mouse strains showed similar gender induced differences in immune cell populations in the mesenteric lymph nodes. Therefore, host-microbe interactions might be more complicated than assumed, as bacterial-species adaptations might be highly dependent on the genetic make-up of the individual.
Sex and strain dependent differences in mucosal immunology and microbiota composition in mice.
Sex, Specimen part
View SamplesA dysbiosis in the intestinal microbiome plays a role in the pathogenesis of several immunological diseases. These diseases often show a gender bias, suggesting gender differences in immune responses and in the intestinal microbiome. We hypothesized that gender differences in immune responses are associated with gender differences in microbiota. We demonstrated mouse strain dependent gender differences in the intestinal microbiome. Interestingly, a cluster of colonic genes (related to humoral and cell-mediated immune responses) correlated oppositely with microbiota species abundant in B6 females and in BALB/c males. This suggests that with different genetic backgrounds, gender associated immune responses are differentially regulated by microbiota. The net result was the same, since both mouse strains showed similar gender induced differences in immune cell populations in the mesenteric lymph nodes. Therefore, host-microbe interactions might be more complicated than assumed, as bacterial-species adaptations might be highly dependent on the genetic make-up of the individual.
Sex and strain dependent differences in mucosal immunology and microbiota composition in mice.
Sex, Specimen part
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 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 Samples