Homo sapiens
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PROVIDER: PRJNA151599 | ENA |
REPOSITORIES: ENA
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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.
2013-01-04 | E-GEOD-35295 | biostudies-arrayexpress
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.
2013-01-04 | GSE35295 | GEO
Project description:Cell surface capture technology data from human pluripotent stem cell derived hepatic endoderm at day 10 of differentiation
2016-10-03 | MSV000080215 | MassIVE
Project description:Human cytomegalovirus (HCMV)has a global distribution and is highly prevalent. HCMV infection has been recognized as a major contributor to neural development abnormalities in embryos and children. However, the underlying mechanisms by which HCMV infection leads to neurological diseases remain incompletely understood. Our study showed that HCMV inhibits neural cell differentiation by affecting the production of adenosine triphosphate (ATP) during neural differentiation. In this work, we found that HCMV infection interferes with the neural differentiation of stem cells from human exfoliated deciduous teeth (SHEDs)and human neuroblastoma cell line (SH-SY5Ys), affects the expression of neural cell markers, and inhibits the axon formation of neural cells. Under neurogenic inductive conditions, HCMV infection of SHEDs and SH-SY5Ys caused an increase in Glycogen synthase kinase-3β(GSK-3β) phosphorylation level and a decrease in GSK-3β phosphatase activity. HCMV infection was shown to inhibits GSK-3β activity, suppresses the level of mitochondrial oxidative phosphorylation in cells, reduces ATP production, impedes energy supply during neural differentiation, and inhibits neural differentiation. Our study sheds light on a molecular mechanism by which crosstalk between protein phosphorylation and oxidative phosphorylation links HCMV infection and neural differentiation and raises a potential strategy for the therapy of congenital HCMV infection.
2025-08-09 | GSE305000 | GEO
Project description:Human Cytomegalovirus Infection Causes Premature and Abnormal Differentiation of Human Neural Progenitor Cells
| PRJNA121723 | ENA
Project description:Temporal dynamics of prenatal brain development are influenced by changes in the microenvironment. Particularly, extracellular proteins contribute to the dynamic niche that balances neural stem cell proliferation and differentiation. Here, we present a resource for proteome and secretome analysis of human induced pluripotent stem cell-derived dorsal forebrain organoids over the early developmental period. We used liquid chromatography-mass spectrometry to identify proteins found in whole organoid and secreted proteins at days 20, 35, and 50 of dorsal forebrain organoid differentiation. We show that the whole organoid proteome demonstrates progression in the neurodevelopmental trajectory with reduced proliferation and increased neural differentiation over time. However, secretome analysis revealed a unique signature for developmental progression. Cell adhesion molecules are enriched in the secretome of day 35 organoids, while secretome of day 50 organoids is enriched with extracellular matrix proteins, demonstrating a change in the extracellular interactions over time of organoid differentiation and maturation. We, therefore, show the relevance of secretome analysis for the thorough study of extracellular matrix-related proteins and the importance of time course study of neural organoids to understand the subtle changes that guide human neurodevelopment.
2024-05-27 | MSV000094878 | MassIVE
Project description:This study examines and compares the protein content in conditioned media collected from neural cell types generated from human pluripotent stem cells. Conditioned media was prepared for 48 hours at a final endpoint of differentiation day 12. Both groups are from parental line WTC11 and cultured as a monolayer on matrigel. Both groups contain a transgene cassette for doxycycline-inducible expression of sox9 and nfia. Doxycycline was only included in the iAstro groups, whereas it was omitted in the neural progenitor cell groups.
2022-01-19 | PXD030821 | Pride
Project description:<p>Familial Dysautonomia (FD) is a developmental and degenerative genetic disease that manifests in the neural crest cells and peripheral nervous system (PNS). Despite all FD patients having the same mutation in <i>IKBKAP</i>, patients present with varying disease severity, ranging from mild to severe. We used the human pluripotent stem cell technology to recapitulate this varying disease severity in the dish. Further, we found that severe, but not mild patients harbor mutations in candidate modifier genes that may contribute to severe disease presentation.</p>
| phs001233 | dbGaP
Project description:The present study evaluated the effects of a repeated-dose exposure of environmentally relevant BPA concentrations during the in vitro 3D neural induction of human induced pluripotent stem cells (hiPSCs), emulating a chronic exposure scenario. Quantitative proteomics at D21 revealed several differentially abundant proteins across all BPA-treated groups with important functions in NSC proliferation and maintenance.
2023-09-06 | PXD042045 | Pride
Project description:The use of pluripotent stem cells in regenerative medicine and disease modeling is complicated by the variation in differentiation properties between lines. In this study, we characterized 13 human embryonic stem cell. (hESC) and 26 human induced pluripotent stem cell (hiPSC) lines to identify markers that predict neural differentiation behavior. At a general level, markers previously known to distinguish mouse ESCs from epiblast stem cells (EpiSCs) correlated with neural differentiation behavior. More specifically, quantitative analysis of miR-371-3 expression prospectively identified hESC and hiPSC lines with differential neurogenic differentiation propensity and in vivo dopamine neuron engraftment potential. Transient KLF4 transduction increased miR-371-3 expression and altered neurogenic behavior and pluripotency marker expression. Conversely, suppression of miR- 371-3 expression in KLF4-transduced cells rescued neural differentiation propensity. miR-371-3 expression level therefore appears to have both a predictive and a functional role in determining human pluripotent stem cell neurogenic differentiation behavior. [mRNA profiling (Illumina)]: Four human ESC lines (H9, I4, I6, HUES6) at undifferentiation stages were purified with stem cell surface marker SSEA4 and subjected to RNA extraction and hybridization on Illumina microarrays. Each sample has 3 biological repeats, one of which has two technical repeats. [miRNA profiling (Agilent)]: Four human ESC lines (H9, I4, I6, HUES6) at undifferentiation stages were purified with stem cell surface marker SSEA4 and subjected to RNA extraction and hybridization on Agilent microarrays. Each sample has 3 biological repeats, one of which has two technical repeats.
2011-06-01 | E-GEOD-27834 | biostudies-arrayexpress