Similar Datasets
Project description:Regulation of brain aging by neutral sphingomyelinase 2
| PRJNA742012 | ENA
Project description:Host cell lipids play a pivotal role in the pathogenesis of respiratory virus infection. However, a direct comparison of the lipidomic profile of influenza virus and rhinovirus infections is lacking. In this study, we first compared the lipid profile of influenza virus and rhinovirus infection in a bronchial epithelial cell line. Most lipid features were downregulated for both influenza virus and rhinovirus, especially for the sphingomyelin features. Pathway analysis showed that sphingolipid metabolism was the most perturbed pathway. Functional study showed that bacterial sphingomyelinase suppressed influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, but promoted rhinovirus replication. These findings suggest that sphingomyelin pathway can be a potential target for antiviral therapy, but should be carefully evaluated as it has opposite effects on different respiratory viruses. Furthermore, the differential effect of sphingomyelinase on rhinovirus and influenza virus may explain the interference between rhinovirus and influenza virus infection.
2022-11-15 | MTBLS2352 | MetaboLights
Project description:Purpose: Identification of the miRNA signature carried by the exosomes released from embryonic hippocampal cells under ceramide treatment Outcome: We investigated the role of ceramide in amplifying the differentiation signal of HN9.10 cells. Treatment of HN9.10 cells with ceramide caused the release of exosomes carrying neutral sphingomyelinase and neutral ceramidase. The analysis of exosomal miRNAs showed that 38 miRNAs were differentially expressed in a statistically significant manner, with some overexpressed miRNAs regulating genes encoding for proteins involved in biological, homeostatic, biosynthetic and small molecule metabolic processes, embryo development and cell differentiation, all phenomena that could be relevant for HN9.10 cell differentiation.
2023-07-12 | GSE228052 | GEO
Project description:Purpose: The goals of this study are to compare next generation sequencing-derived brain cortex transcriptome profiling (RNA-seq) to study the role of neutral sphingomyelinase 2 (smpd3) in brain aging. Methods: Brain cortex mRNA profiles of 10 month old (fro/+) and smpd3 total knockout (fro/fro) mice were generated by deep sequencing, in duplicate, using Illumina NovaSeq 6000. (https://en.novogene.com) Results:A total of 1462 transcripts differed between genotypes, with 891 transcripts increased and 571 transcripts decreased. Conclusions: Transcriptome differences link decreased oxidative stress and astrocyte activation in brain cortex to nSMase2 deficiency, while synaptic signaling transcripts increased in ways consistent with increased cognitive function previously demonstrated in nSMase2-deficient mice.
2022-04-27 | GSE179045 | GEO
Project description:FAN (Factor associated with neutral sphingomyelinase activation) is an adaptor protein that constitutively binds to TNF-R1. Microarray analysis was performed in fibroblasts derived from wild-type or FAN knockout mouse embryos to evaluate the role of FAN in TNF-induced gene expression. We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process. Keywords: genetic modification
2009-08-31 | GSE12275 | GEO
Project description:Genome-wide maps of gene expression in alkaline sphingomyelinase knockout mice
| PRJNA471908 | ENA
Project description:Several neurodevelopmental processes including neuronal survival, migration and differentiation are controlled by sphingolipid metabolism. Sphingomyelin is an abundant component of cell membranes. Sphingomyelinases generate ceramide from sphingomyelin as a second messenger in intracellular signaling pathways involved in cell proliferation, differentiation, or apoptosis. While the role of acid sphingomyelinase is well established, the role of neutral sphingomyelinases in human neurodevelopment has remained elusive. Twenty-five children from ten unrelated families presented with microcephaly with simplified gyral pattern, cerebellar hypoplasia, severe developmental encephalopathy, congenital arthrogryposis, diabetes mellitus and early fetal/-postnatal demise. All probands tested have biallelic loss of function variants in SMPD4, coding for neutral sphingomyelinase-3 (nSMase-3 / SMPD4). Fibroblasts from affected individuals showed morphologic endoplasmic reticulum (ER) cisternae abnormalities and increased autophagy, consistent with a previously suggested function of SMPD4 in the ER. Overexpression of human Myc-tagged SMPD4 in HEK293T cells showed localization to both the outer nuclear envelope and the ER. Previous studies localized SMPD4 to the outer nuclear membrane. Mass spectrometry of SMPD4-associated proteins detected peptides belonging to nuclear pore complex proteins. After downregulation of SMPD4 by siRNA, delayed cell cycle progression was observed and primary fibrobalsts from affected individuals were more prone to apoptosis than controls. These data are consistent with former studies in HeLa cells showing mitotic abnormalities after siSMPD4 treatment. This study provides a link between sphingolipid membrane homeostasis, cell fate and mitotic decisions indicating novel pathway in the pathogenesis of microcephaly.
2019-12-31 | GSE133264 | GEO
Project description:SMPD4 (neutral sphingomyelinase-3/nSMase3) has recently been shown to be a new cause of microcephaly in a cohort of twenty-three pediatric patients. The function of nSMases in brain development and how SMPD4 variants cause human microcephaly and cerebellar hypoplasia was previously unknown.We developed an iPSC model to complement our mouse study. We found iPSC models from human SMPD4 patient and CRISPR/Cas9-induced SMPD4 knockout lines demonstrate a proliferation defect, increased cell death, loss of neural progenitors, and shortened primary cilia. Treatment with exogenous ceramide significantly rescues the cilia defect. SMPD4 patient and knockout cells have altered WNT signaling. We provide evidence that SMPD4 controls brain development by providing ceramide for primary ciliogenesis, suggesting a novel therapeutic strategy for SMPD4 mediated disease.
2023-12-24 | GSE250472 | GEO
Project description:Genome-wide maps of gene expression in liver of alkaline sphingomyelinase knockout mice
| PRJNA527215 | ENA
Project description:RNA transfer via extracellular vesicles (EVs) influences cell phenotypes; however, lack of information regarding biogenesis of RNA-containing EVs has limited progress in the field. Here, we identify endoplasmic reticulum membrane contact sites (ER MCS) as platforms for generation of RNA-containing EVs. We identify a subpopulation of small EVs that is highly enriched in RNA and regulated by the ER MCS linker protein VAP-A. Functionally, VAP-A-regulated EVs are critical for miR-100 transfer between cells and in vivo tumor formation. Lipid analysis of VAP-A-knockdown EVs revealed reductions in the EV biogenesis lipid ceramide. Knockdown of the VAP-A-binding ceramide transfer protein CERT led to similar defects in EV RNA content. Imaging experiments revealed that VAP-A promotes lumenal filling of multivesicular bodies (MVBs). CERT localizes to MVBs, and the ceramide-generating enzyme neutral sphingomyelinase 2 colocalizes with VAP-A-positive ER. We propose that ceramide transfer via VAP-A-CERT linkages drives biogenesis of a select RNA-containing population.
2022-04-05 | GSE188223 | GEO