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HCMV infection of human neural precursor cells: Human neural precursor cell expression

ABSTRACT: HCMV -treated and control human adult neural precurso cells (NPC) were used to extract RNA for profiling on DNA arrays Primary adult hippocampus-derived neural precursor cells were used at passage # 2-4 for HCMV infection, followed by RNA extraction at indicated times

ORGANISM(S): Homo sapiens

PROVIDER: GSE30912 | GEO | 2012/07/22

SECONDARY ACCESSION(S): PRJNA154607

REPOSITORIES: GEO

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HCMV infection of human neural precursor cells: Human neural precursor cell expression

Project description:HCMV -treated and control human adult neural precurso cells (NPC) were used to extract RNA for profiling on DNA arrays Primary adult hippocampus-derived neural precursor cells were used at passage # 2-4 for HCMV infection, followed by RNA extraction at indicated times Primary adult neural precursor cells were infected with HCMV strains Towne and TR (O.1MOI) and RNA was extracted at 72 hrs postinfection for expression profiling on both HCMV and Affymetrix DNA arrays

2012-07-21 | E-GEOD-30912 | biostudies-arrayexpress

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Project description:Congenital human cytomegalovirus (HCMV) infection is one of the leading prenatal causes of mental retardation and congenital deformities world-wide. Access to cultured human neuronal lineages, necessary to understand the species specific pathogenic effects of HCMV has been limited by difficulties in sustaining primary cultures. Neuronal cells derived from human induced pluripotent stem (iPS) cells now provide a novel opportunity to investigate HCMV pathogenesis. We derived iPS cells from human adult fibroblasts and induced neural lineages to investigate their permissiveness to infection with HCMV strain Ad169. Analysis of iPS cells and nearly pure populations of iPS-derived neural stem cells (NSCs), neuroprogenitor cells (NPCs) and neurons suggests that (i) iPS cells are not permissive to HCMV infection; (ii) Neural stem cells have impaired differentiation when infected by HCMV; (iii) NPCs are fully permissive for HCMV infection; the supernatant from infected neural stem cells and NPCs (but not mock infected cells) induced cytopathic effects in human fibroblasts; (iv) most iPS-derived neurons are not permissive to HCMV infection; and (v) infected neurons have impaired calcium influx in response to glutamate. Our approach offers powerful cellular models to investigate the effect of neurotropic viral agents on human neurodevelopment. Adherent monolayer culture of neural progenitor cells (NPCs) were either infected with HCMV Ad169 in triplicate, with each individual sample harvested separately to provide biological replicates for expression analysis. Infected and mock-infected cells were harvested 24 h p.i. RNA. NPCs were 70-80% confluence.

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Human cytomegalovirus infection perturbs neural progenitor cell fate via the expression of viral microRNAs

Project description:Congenital human cytomegalovirus (HCMV) infection is the leading infectious cause of birth defects, including neurodevelopmental disorders. HCMV infection mainly targets neural progenitor cells (NPCs) in fetal brains, inducing abnormal differentiation by altering key regulatory pathways. HCMV expresses a series of viral miRNAs during infection, but their roles, particularly in NPCs, are not fully understood. In this study, we characterized expression profiles of both cellular and viral miRNAs in HCMV-infected NPCs by microarray analysis during early infection time points and investigated the primary effects of these miRNAs on regulating NPC fate. While expression of most cellular miRNAs was unaffected by HCMV infection, one cellular miRNA was upregulated and six were downregulated from 2 to 24 h post infection. Moreover, of 17 HCMV miRNAs evaluated, six were differentially expressed in HCMV-infected NPCs during early infection time points.

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Project description:The lateral ventricle subventricular zone (SVZ) is a frequent and consequential site of pediatric and adult glioma spread, but the cellular and molecular mechanisms mediating this are poorly understood. We demonstrate that neural precursor cell (NPC):glioma cell communication underpins this propensity of glioma to colonize the SVZ through secretion of chemoattractant signals toward which glioma cells home. Biochemical, proteomic, and functional analyses of SVZ NPC-secreted factors revealed the neurite outgrowth-promoting factor pleiotrophin, along with required binding partners SPARC/SPARCL1 and HSP90B, as key mediators of this chemoattractant effect. Pleiotrophin expression is strongly enriched in the SVZ, and pleiotrophin knockdown starkly reduced glioma invasion of the SVZ in the murine brain. Pleiotrophin, in complex with the binding partners and signaling through the receptor PTPRZ1, activated glioma Rho/ROCK signaling, and ROCK inhibition decreased invasion toward SVZ NPC-secreted factors. These findings demonstrate a pathogenic role for NPC:glioma interactions and potential therapeutic targets to limit glioma invasion.

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HCMV infection of human neural precursor cells

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