Similar Datasets
Project description:The ChIP-seq and RNA-seq data provide evidence that ZIKV-NS5 binds to the gene body of the key neuro-factors and then inhibits their transcription, thus disrupting the neurogenesis of human NPCs.
2022-01-27 | GSE165893 | GEO
Project description:Among the flaviviral proteins, NS5 is the largest and most conserved. NS5 contains major enzymatic components of the viral replication complex. Disruption of the common key NS5-host protein-protein interactions critical for viral replication could aid in the development of broad-spectrum anti-flaviviral therapeutics. To this end, we investigated the JEV- and ZIKV-NS5 interactomes in human cells using GFP pull-downs with mass spectrometry analysis in a label-free fashion. A total of 138 cellular proteins interacting with NS5 from JEV, ZIKV, or both were identified as Protein classification analysis of identified cellular targets revealed the enrichment of RNA binding, processing and splicing including spliceosomal and spliceosome-associated proteins in both datasets. Comparison of our data with literature not only revealed several cellular NS5 interacting proteins shared among flaviviruses, but also identified proteins that have no known function in flavivirus biology such as RNA polymerase II-associated Paf1 complex, protein phosphatase 6, and s-adenosylmethionine synthetase. Our study generates the first landscape of the JEV and ZIKV NS5 interactome in human cells and identifies cellular proteins that are potentially targetable for broad-spectrum anti-flaviviral therapy.
2022-05-04 | PXD009523 | Pride
Project description:RNA-seq of detecting the effect of NS5 for neurogenesis.
| PRJNA694842 | ENA
Project description:ZIKV NS5 WT expression in human brain microvascular endothelical cells (hBMECs) alters transcriptional responses and downregulate genes related to cell cycle, nucleosome formation and interferon stimulated genes (ISGs).
2020-04-02 | GSE147926 | GEO
Project description:Growing evidences have associated Zika virus infection with congenital malformations, including microcephaly. Nonetheless, signaling mechanisms that promote the disease outcome are far from being understood, affecting the development of suitable therapeutics. In this study, we applied shotgun mass spectrometry-based proteomics combined with cell biology approaches to characterize altered molecular pathways on neurons and NPCs infected by ZIKV-BR, strain obtained from the 2015 Brazilian outbreak. Assessment of neurons differentiated from iPSC from different donors shows the importance of the host genetic background to the susceptibility of ZIKV infection, also confirmed by cytokine fingerprinting. Additionally, infected cells presented an impairment of neurogenesis and synaptogenesis processes. Moreover, ZIKV-BR infected NPCs showed unique alteration of pathways involved in neurological diseases, cell death and survival and embryonic development compared to ZIKV-AF, showing a human adaptation of the Brazilian viral strain. Taken together, these data explain CNS developmental arrest observed in Congenital Zika Virus syndrome is beyond neuronal cell death.
2019-11-12 | PXD009293 | Pride
Project description:Physical exercise stimulates adult hippocampal neurogenesis in mammals, and is considered a relevant strategy for preventing age-related cognitive decline in aging humans. However, its mechanism is controversial. Here, by investigating microRNAs (miRNAs) and their downstream pathways, we uncover that downregulation of miR-135a-5p mediates exercise-induced proliferation of adult NPCs in adult neurogenesis in the mouse hippocampus, likely by activation of phosphatidylinositol (IP3) signaling. Specifically, while overexpression of miR-135 prevents exercise-induced proliferation in the adult mouse hippocampus in vivo and in NPCs in vitro, its inhibition activates NPCs proliferation in resting and aged mice. Label free proteomics and bioinformatics analysis identifies 11 potential targets of miR-135 in NPCs, several of them involved in phosphatidylinositol signaling. Thus, miR-135a is key in mediating exercise-induced adult neurogenesis and opens intriguing perspectives toward the therapeutic exploitation of miR-135 to delay or prevent pathological brain ageing.Physical exercise stimulates adult hippocampal neurogenesis in mammals, and is considered a relevant strategy for preventing age-related cognitive decline in aging humans. However, its mechanism is controversial. Here, by investigating microRNAs (miRNAs) and their downstream pathways, we uncover that downregulation of miR-135a-5p mediates exercise-induced proliferation of adult NPCs in adult neurogenesis in the mouse hippocampus, likely by activation of phosphatidylinositol (IP3) signaling. Specifically, while overexpression of miR-135 prevents exercise-induced proliferation in the adult mouse hippocampus in vivo and in NPCs in vitro, its inhibition activates NPCs proliferation in resting and aged mice. Label free proteomics and bioinformatics analysis identifies 11 potential targets of miR-135 in NPCs, several of them involved in phosphatidylinositol signaling. Thus, miR-135a is key in mediating exercise-induced adult neurogenesis and opens intriguing perspectives toward the therapeutic exploitation of miR-135 to delay or prevent pathological brain ageing.
2019-11-12 | PXD009845 | Pride
Project description:Neural stem cells (NSCs) and progenitor cells (NPCs) are increasingly appreciated to hold great promise for regenerative medicine to treat CNS injuries and neurodegenerative diseases. However, evidence for effective stimulation of neuronal production from endogenous or transplanted NPCs for cell replacement with small molecules remains limited. To identify novel chemical entities/targets for neurogenesis, we had established a NPC phenotypic screen assay and validated it using known small-molecule neurogenesis inducers. Through screening small molecule libraries with annotated targets, we identified BET bromodomain inhibition as a novel mechanism for enhancing neurogenesis. BET bromodomain proteins, Brd2, Brd3, and Brd4 were found to be downregulated in NPCs upon differentiation, while their levels remain unaltered in proliferating NPCs. Consistent with the pharmacological study using bromodomain selective inhibitor (+)-JQ-1, knockdown of each BET protein resulted in an increase in the number of neurons with simultaneous reduction in both astrocytes and oligodendrocytes. Gene expression profiling analysis demonstrated that BET bromodomain inhibition induced a broad but specific transcription program enhancing directed differentiation of NPCs into neurons while suppressing cell cycle progression and gliogenesis. Together, these results highlight a crucial role of BET proteins as promising epigenetic regulators in NPC development and suggest a therapeutic potential of BET inhibitors in treating CNS injury and neurodegenerative diseases. NPCs were treated with (+)-JQ-1 or inactive enantiomer (-)-JQ-1 at 0.2 μM or 0.5 μM for 12 and 24 hrs in differentiation medium. The experiments were carried out in 3 independent preparations of NPCs (triplicates)
2016-07-24 | E-GEOD-77988 | biostudies-arrayexpress
Project description:We use ChIP-seq on PAF1C member Leo1 to determine how PAF1C occupancy at interferon stimulated genes is impacted by dengue virus NS5 protein.
2018-12-03 | GSE110511 | GEO
Project description:Gene expression in NS5 murine neural stem cells was compared to that of astrocytes derived from NS5 cells via 3 days of treatment with foetal calf serum (FCS). Keywords: cell type comparison
2009-12-31 | GSE10721 | GEO