Mus musculus
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ABSTRACT:
PROVIDER: PRJNA354944 | ENA |
REPOSITORIES: ENA
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Project description:Neuronal activity, TGFβ signaling and unpredictable chronic stress affect transcription of Gadd45 family members in vitro and in vivo
| PRJNA354940 | ENA
Project description:Neuronal activity, TGFβ signaling and unpredictable chronic stress affect transcription of Gadd45 family members in vitro and in vivo [Affymetrix]
| PRJNA354945 | ENA
Project description:Neuronal activity is altered in several neurological and psychiatric diseases. Upon depolarization not only neurotransmitters are released but also cytokines and other activators of signaling cascades. Unraveling their complex implication in transcriptional control in receiving cells will contribute to understand specific central nervous system (CNS) pathologies and will be of therapeutical interest. In this study we depolarized mature hippocampal neurons in vitro using KCl and revealed increased release not only of Brain-derived neurotrophic factor (BDNF), but also of Transforming growth factor beta (TGFB). Neuronal activity together with BDNF and TGFB controls transcription of DNA modifying enzymes specifically members of the DNA-damage-inducible (Gadd) family, Gadd45a, Gadd45b, and Gadd45g. MeDIP followed by massive parallel sequencing and transcriptome analyses revealed less DNA methylation upon KCl treatment. Thereby, psychiatric disorder-related genes, namely Tshz1, Foxn3, Jarid2, Per1, Map3k5, and Arc are transcriptionally activated and demethylated upon neuronal activation. To analyze whether misexpression of Gadd45 family members can be associated with psychiatric diseases, we applied unpredictable chronic mild stress (UCMS) as established model for depression to mice.UCMS lead to a reduced expression of Gadd45 family members. Taken together, our data demonstrate that Gadd45 family members are new putative targets for UCMS treatments.
2017-12-31 | GSE90509 | GEO
Project description:Neuronal activity is altered in several neurological and psychiatric diseases. Upon depolarization not only neurotransmitters are released but also cytokines and other activators of signaling cascades. Unraveling their complex implication in transcriptional control in receiving cells will contribute to understand specific central nervous system (CNS) pathologies and will be of therapeutical interest. In this study we depolarized mature hippocampal neurons in vitro using KCl and revealed increased release not only of Brain-derived neurotrophic factor (BDNF), but also of Transforming growth factor beta (TGFB). Neuronal activity together with BDNF and TGFB controls transcription of DNA modifying enzymes specifically members of the DNA-damage-inducible (Gadd) family, Gadd45a, Gadd45b, and Gadd45g. MeDIP followed by massive parallel sequencing and transcriptome analyses revealed less DNA methylation upon KCl treatment. Thereby, psychiatric disorder-related genes, namely Tshz1, Foxn3, Jarid2, Per1, Map3k5, and Arc are transcriptionally activated and demethylated upon neuronal activation. To analyze whether misexpression of Gadd45 family members can be associated with psychiatric diseases, we applied unpredictable chronic mild stress (UCMS) as established model for depression to mice.UCMS lead to a reduced expression of Gadd45 family members. Taken together, our data demonstrate that Gadd45 family members are new putative targets for UCMS treatments.
2017-12-31 | GSE90508 | GEO
Project description:Isogenic hESC clones with and without the FX mutation that share the same genetic background were in vitro differentiated into neurons. FX neurons present delayed neuronal development and maturation with full FMRP silencing. Following enrichment of neurons in the culture by MACS, transcriptome analysis by RNA sequencing at different time points during differentiation demonstrated dysregulation of the TGFβ/BMP signaling pathway and genes related to the extracellular matrix. FX neurons showed decreased neurite outgrowth that was rescued by inhibition of the TGFβ/BMP signaling pathway, this treatment did not affect the outgrowth of control neurons. In FMRP expressing neurons the regulation of the TGFβ/BMP pathway allow typical neurite outgrowth and axonogenesis that will eventually result in normal neuronal network activity. In contrast, in FX neurons the lack of FMRP dysregulate members of the BMP signaling pathway associated with the ECM organization that in a yet unknown mechanism, reduces the guidance of axonal growth cones, leading to an aberrant neuronal network function. Overall, our results provide new insights into the molecular pathways by which loss of FMRP affects neuronal network development which probably leads to its aberrant function in FXS.
2022-08-31 | GSE206088 | GEO
Project description:TGFβ is one of most intensively studied regulators of extracellular matrix formation, and has been implicated in the development of pulmonary fibrosis in different models. However, little is know about the role of miRNAs in TGFβ mediated fibrogenic gene regulation. By using miRNA qRT-PCR array, we have identified miRNAs whose expression are regulated by TGFβ in IMR-90 cells. Among those down-regulated miRNAs are miR-29 family members. Knockdown miR-29 in IMR-90 cells results in up-regulation of a large number of extracellular matrix and fibrogenic genes including family members of collagen, laminin, integrin, ADAM and MMP, many of them are predicted or confirmed miR-29 targets. Hierarchichal clustering analysis of mRNA array data revealed that many extracellular matrix and fibrogenic genes up-regulated by TGFβ in IMR-90 cells, are also up-regulated in miR-29 KD cells. Moreover, the similar set of extracellular matrix and fibrogenic genes is also significantly up-regulated in bleomycin treated mouse lungs. Together, our data strongly suggest that downstream of the TGFβ, miR-29 is a master modulator of genes involved in extracellular matrix formation and might play a significant role in pulmonary fibrosis.
2010-03-01 | GSE18651 | GEO
Project description:Metronidazole and ciprofloxacin differentially affect chronic unpredictable mild stress-induced changes in colon, cecum and ileum microbiome
| PRJNA745005 | ENA
Project description:The goals of this study are to compare NGS in 3day post fertilized zebrafish embryo after knockout terfa (telomere repeats binding factor 2). In order to investigate the role of terfa in DDR, telomere protection and neuro-development. Using an optimized data analysis workflow, we mapped about 30 million sequence reads per sample to the zebrafish genome (build zv10) and identify 8840 NGS in 'WT vs terfa-/-' group and 4137 NGS in 'WT vs terfa+/-' group. Our results indicate that zebrafish terfa involved in 1. cell cycle dysregulation (e.g. senescence, p53, spliceosome, RNA transport, Ribosome, mRNA surveillance and cell cycles), including an increased expression of two p53-targeted genes, cdkn1a (p21) and gadd45; 2. inflammation (e.g. Salmonella and Herpes simplex infections, TOL-like receptor signaling and Cell Adhesion), including an increased expression of two pro-inflammatory genes, il6 and isg15. 3. neuronal dysfunction (e.g. Phototransduction, Calcium signaling and Neuroactive ligand-receptor interaction), including a signature of glial injury (gfap, ctsl, metrn, gcm2, clu and 5 members of the slc1a family (3, 4, 5, 7, 8)).
2022-03-09 | GSE173639 | GEO
Project description:In this study we employed the chronic unpredictable stress (CUS) rat model that leads to anxiety features comparable to humans and validated in several published reports as a well-characterized model of depression symptoms with high predictive validity. Cytokines and activated intracellular kinase levels were determined using high throughput multiplex assays. RNA from freshly isolated adipocytes was used to run whole genome expression microarray profiling in control and stressed rats. Adipocyte function was assessed via tritiated glucose uptake assay. The expression of four cytokines (TNFα, IL-1β, IL-6 and MCP-1) was validated via real-time PCR and the all showed increased expression levels with chronic unpredictable stress. Male rats were subjected to chronic unpredictable stress for 35 days and total body fat was measured. The analyses presented here represents data from experiments performed in 6 control and 6 stressed rats in parallel. All cells for RNA isolation were collected at the conclusion of the 35 day stress protocol.
2014-06-03 | E-GEOD-47754 | biostudies-arrayexpress
Project description:Methylated DNA immunoprecipitation followed by high-throughput sequencing (MeDIP-seq) has the potential to identify changes in DNA methylation important in cancer development. In order to understand the role of epigenetic modulation in the development of acute myeloid leukemia (AML) we have applied MeDIP-seq to the DNA of 12 AML patients and 4 normal bone marrows. This analysis revealed leukemia-associated differentially methylated regions that included gene promoters, gene bodies, CpG islands and CpG island shores. Two genes (SPHKAP and DPP6) with significantly methylated promoters were of interest and further analysis of their expression showed them to be repressed in AML. We also demonstrated considerable cytogenetic subtype specificity in the methylomes affecting different genomic features. Significantly distinct patterns of hypomethylation of certain interspersed repeat elements were associated with cytogenetic subtypes. The methylation patterns of members of the SINE family tightly clustered all leukemic patients with an enrichment of Alu repeats with a high CpG density (P < 0.0001). We were able to demonstrate significant inverse correlation between intragenic interspersed repeat sequence methylation and gene expression with SINEs showing the strongest inverse correlation (R2 = 0.7). We conclude that the alterations in DNA methylation that accompany the development of AML affect not only the promoters, but also the non-promoter genomic features, with significant demethylation of certain interspersed repeat DNA elements being associated with AML cytogenetic subtypes. MeDIP-seq data were validated using bisulfite pyrosequencing and the Infinium array. Examination of DNA methylation of 12 AML patients versus normal bone marrow from 4 healthy donors
2012-04-02 | E-GEOD-28314 | biostudies-arrayexpress