The Neurotoxin DSP-4 Dysregulates the Locus Coeruleus-Norepinephrine System and Recapitulates Molecular and Behavioral Aspects of Prodromal Neurodegenerative Disease
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE221404 | GEO | 2022/12/26
REPOSITORIES: GEO
Similar Datasets
Project description:To investigate changes in noradrenergic neurons of the LC following infusion of human Tyrosinase (hTyr) We performed gene expression profiling analysis using data obtained from RNA-seq of Pre-IP and IP samples following hTyr or EYFP infusion into the LC.
2023-03-17 | GSE226827 | GEO
Project description:Background: The goal of this study was to determine the transcriptional consequences of norepinephrine transporter (NET) gene deletion in noradrenergic neuron differentiation. The norepinephrine transporter (NET) is the target of powerful mind-altering substances, such as tricyclic antidepressants and the drug of abuse, cocaine. NET function in adult noradrenergic neurons of the peripheral and central nervous systems is that of a scavenger that internalizes norepinephrine from the synaptic cleft. By contrast, norepinephrine (NE) transport has a different role in embryogenesis. It promotes differentiation of neural crest cells and locus ceruleus progenitors into noradrenergic neurons, whereas NET inhibitors, such as the tricyclic antidepressant desipramine and the drug of abuse, cocaine, inhibit noradrenergic differentiation. While NET structure und regulation of NET function is well described, little is known about downstream targets of NE transport. Results: We have determined by long serial analysis of gene expression (LongSAGE) the gene expression profiles of in vitro differentiating wild type and norepinephrine transporter-deficient (NETKO) neural crest derivatives. Comparison analyses with the wild type library (GSM 105765) have identified a number of important differentially expressed genes, including genes relevant to noradrenergic neuron differentiation and to the phenotype of NETKO mice. Furthermore we have identified novel differentially expressed genes. Conclusions: Loss of NET function during embryonic development deregulates signaling pathways that are critically involved in neural crest formation and noradrenergic neuron differentiation. The library was constructed from total RNA of 60 neural crest culture at culture day 7. The neural tubes were dissected from E9.5 embryos that lack the norepinephrine transporter gene.
2008-06-23 | E-GEOD-11788 | biostudies-arrayexpress
Project description:Background: The goal of this study was to determine the transcriptional consequences of norepinephrine transporter (NET) gene deletion in noradrenergic neuron differentiation. The norepinephrine transporter (NET) is the target of powerful mind-altering substances, such as tricyclic antidepressants and the drug of abuse, cocaine. NET function in adult noradrenergic neurons of the peripheral and central nervous systems is that of a scavenger that internalizes norepinephrine from the synaptic cleft. By contrast, norepinephrine (NE) transport has a different role in embryogenesis. It promotes differentiation of neural crest cells and locus ceruleus progenitors into noradrenergic neurons, whereas NET inhibitors, such as the tricyclic antidepressant desipramine and the drug of abuse, cocaine, inhibit noradrenergic differentiation. While NET structure und regulation of NET function is well described, little is known about downstream targets of NE transport. Results: We have determined by long serial analysis of gene expression (LongSAGE) the gene expression profiles of in vitro differentiating wild type and norepinephrine transporter-deficient (NETKO) neural crest derivatives. Comparison analyses with the wild type library (GSM 105765) have identified a number of important differentially expressed genes, including genes relevant to noradrenergic neuron differentiation and to the phenotype of NETKO mice. Furthermore we have identified novel differentially expressed genes. Conclusions: Loss of NET function during embryonic development deregulates signaling pathways that are critically involved in neural crest formation and noradrenergic neuron differentiation.
2008-06-23 | GSE11788 | GEO
Project description:The neurotoxin MPP+ triggers cell death of dopamine neurons and induces Parkinson’s disease symptoms in mice and men, but the immediate transcriptional response to this neurotoxin has not been studied. We therefore treated human SH-SY5Y cells with a low dose (0.1 mM) of MPP+ and measured the effect on nascent transcription by precision run-on sequencing (PRO-seq). We found that transcription of the mitochondrial genome was significantly reduced already after 30 min, whereas nuclear gene transcription was unaffected. Inhibition of respiratory complex I by MPP+ led to reduced ATP production, that may explain the diminished activity of mitochondrial RNA polymerase. Our results show that MPP+ has a direct effect on mitochondrial function and transcription, and that other gene expression or epigenetic changes induced by this neurotoxin are secondary effects that reflect a cellular adaptation program.
2023-06-01 | GSE214243 | GEO
Project description:Botulinum neurotoxin type A (BoNT/A) is one of the most potent protein toxins, which makes it a possible biological weapon and therapeutic. Using microarray analysis we performed global transcriptional profiling of RAW264.7 cells, a murine alveolar macrophage cell line. Time dependent expression profiles after treatment of 1nM or 5nM Botulinum neurotoxin A
2014-12-20 | E-GEOD-64390 | biostudies-arrayexpress
Project description:We developed a new method to extract open-chromatins that contain trans-acting factors (TAFs)-DNA complex crosslinked with dithiobis(succinimidyl propionate) (DSP). Using this method we identified CBFB as a cell density-sensitive TAF, which translocates between the cytoplasm and the nucleus in cell density-dependent manner. Here, we demonstrate that the extracted TAF/DNA complex is also amenable to ChIP-seq analysis.
2023-12-05 | GSE234731 | GEO
Project description:To further characterized the serrated pathway, we used the novel Digital Spatial Profiling (DSP) technology and its mRNA Cancer Transcriptome Atlas (CTA) panel, which includes over 1800 target gene, to investigate the underlying gene expression changes and pathways involved in sessile serrated lesion (SSL) and traditional serrated adenoma (TSA), two precancerous lesions to carcinoma in serrated pathway.
2023-12-31 | E-MTAB-12465 | biostudies-arrayexpress
Project description:We performed single cell transcriptomic profiling of induced human pluripotent stem cells (iPSCs)-derived type 2 alveolar epithelial cells (iAT2). iPSCs stably expressed CRISPRi (dCas9-KRAB) under the control of doxycyline. iAT2s were transduced with a lentivirus expressing gRNA targeting the transcriptional start site of DSP. Cells were treated with or without doxycyline to intiate CRISPRi-knockdown. Prior to capture, cells were labelled with hashing antibodies (HTO). Cells were captured for 10x Genomics Single cell capture (V3 protocol), and GEX and HTO libraries were sequenced. HTODemux function was used to demultiplex the samples. Knockdown of DSP caused cells to cluster separately from wild-type cells.
2022-05-26 | GSE189068 | GEO
Project description:Botulinum neurotoxin type A (BoNT/A) is one of the most potent protein toxins, which makes it a possible biological weapon and therapeutic. Using microarray analysis we performed global transcriptional profiling of RAW264.7 cells, a murine alveolar macrophage cell line.
2014-12-20 | GSE64390 | GEO