Three human glioma stem cell lines sorted for CD133 and one human neural precursor line sorted for CD133 to identify tumor-specific miRNA dysregulation
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Abounader Roger
PROVIDER: S-ECPF-GEOD-49470 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:Several novel potential oncogenic and tumor suppressor miRNAs were identified by using the appropriate controls for stem cells. Expression profiles for human miRNAs in six samples were generated.
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Project description:Several novel potential oncogenic and tumor suppressor miRNAs were identified by using the appropriate controls for stem cells. Expression profiles for human miRNAs in six samples were generated. The Agilent platform GPL7731 was used to analyze six RNA samples: CD133- human NPC, CD133+ human NPC, CD133- B4 glioma, CD133+ B4 Glioma, CD133+ NCH441 glioma, CD133+ NCH644 glioma
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Project description:Adverse effect of alcohol on neural function has been well documented. Especially, the teratogenic effect of alcohol on neurodevelopment during embryogenesis has been demonstrated in various models, which could be a pathologic basis for fetal alcohol spectrum disorders (FASDs). While the developmental defects from alcohol abuse during gestation have been described, the specific mechanisms by which alcohol mediates these injuries have yet to be determined. Recent studies have shown that alcohol has significant effect on molecular and cellular regulatory mechanisms in embryonic stem cell (ESC) differentiation including genes involved in neural development. To test our hypothesis that alcohol induces molecular alterations during neural differentiation we have derived neural precursor cells from pluripotent human ESCs in the presence or absence of ethanol treatment. Genome-wide transcriptomic profiling identified molecular alterations induced by ethanol exposure during neural differentiation of hESCs into neural rosettes and neural precursor cell populations. The Database for Annotation, Visualization and Integrated Discovery (DAVID) functional analysis on significantly altered genes showed potential ethanol's effect on JAK-STAT signaling pathway, neuroactive ligand-receptor interaction, Toll-like receptor (TLR) signaling pathway, cytokine-cytokine receptor interaction and regulation of autophagy. We have further quantitatively verified ethanol-induced alterations of selected candidate genes. Among verified genes we further examined the expression of P2RX3, which is associated with nociception, a peripheral pain response. We found ethanol significantly reduced the level of P2RX3 in undifferentiated hESCs, but induced the level of P2RX3 mRNA and protein in hESC-derived NPCs. Our result suggests ethanol-induced dysregulation of P2RX3 along with alterations in molecules involved in neural activity such as neuroactive ligand-receptor interaction may be a molecular event associated with alcohol-related peripheral neuropathy of an enhanced nociceptive response.
| S-EPMC5040434 | biostudies-literature
Project description:Given the very substantial heterogeneity of most human cancers, it is likely that most cancer therapeutics will be active in only a small fraction of any population of patients. As such, the development of new therapeutics, coupled with methods to match a therapy with the individual patient, will be critical to achieving significant gains in disease outcome. One such opportunity is the use of expression signatures to identify key oncogenic phenotypes that can serve not only as biomarkers but also as a means of identifying therapeutic compounds that might specifically target these phenotypes. Given the potential importance of targeting tumors exhibiting a stem-like phenotype, we have developed an expression signature that reflects common biological aspects of various stem-like characteristics. The Consensus Stemness Ranking (CSR) signature is upregulated in cancer stem cell enriched samples, at advanced tumor stages and is associated with poor prognosis in multiple cancer types. Using two independent computational approaches we utilized the CSR signature to identify clinically useful compounds that could target the CSR phenotype. In vitro assays confirmed selectivity of several predicted compounds including topoisomerase inhibitors and resveratrol towards breast cancer cell lines that exhibit a high-CSR phenotype. Importantly, the CSR signature could predict clinical response of breast cancer patients to a neoadjuvant regimen that included a CSR-specific agent. Collectively, these results suggest therapeutic opportunities to target the CSR phenotype in a relevant cohort of cancer patients. CD133+ and CD133- cells were separated from two glioma xenograft tumors. Both CD133+ and CD133- glioma cells were cultured in serum-free media for 48 hours in the presence of absence of laminin.
| S-ECPF-GEOD-24716 | biostudies-other
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 knock down starkly reduced glioma invasion of the SVZ in the murine brain. Pleiotrophin, in complex with the binding partners, 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. PAPERCLIP.
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Project description:Expression data of Glioma Stem Cells sorted for CD133 and PDPN expression.
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Project description:Given the very substantial heterogeneity of most human cancers, it is likely that most cancer therapeutics will be active in only a small fraction of any population of patients. As such, the development of new therapeutics, coupled with methods to match a therapy with the individual patient, will be critical to achieving significant gains in disease outcome. One such opportunity is the use of expression signatures to identify key oncogenic phenotypes that can serve not only as biomarkers but also as a means of identifying therapeutic compounds that might specifically target these phenotypes. Given the potential importance of targeting tumors exhibiting a stem-like phenotype, we have developed an expression signature that reflects common biological aspects of various stem-like characteristics. The Consensus Stemness Ranking (CSR) signature is upregulated in cancer stem cell enriched samples, at advanced tumor stages and is associated with poor prognosis in multiple cancer types. Using two independent computational approaches we utilized the CSR signature to identify clinically useful compounds that could target the CSR phenotype. In vitro assays confirmed selectivity of several predicted compounds including topoisomerase inhibitors and resveratrol towards breast cancer cell lines that exhibit a high-CSR phenotype. Importantly, the CSR signature could predict clinical response of breast cancer patients to a neoadjuvant regimen that included a CSR-specific agent. Collectively, these results suggest therapeutic opportunities to target the CSR phenotype in a relevant cohort of cancer patients.
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Project description:Converging evidence indicates that microRNAs (miRNAs) may contribute to disease risk for schizophrenia (SZ). We show that microRNA-9 (miR-9) is abundantly expressed in control neural progenitor cells (NPCs) but also significantly downregulated in a subset of SZ NPCs. We observed a strong correlation between miR-9 expression and miR-9 regulatory activity in NPCs as well as between miR-9 levels/activity, neural migration, and diagnosis. Overexpression of miR-9 was sufficient to ameliorate a previously reported neural migration deficit in SZ NPCs, whereas knockdown partially phenocopied aberrant migration in control NPCs. Unexpectedly, proteomic- and RNA sequencing (RNA-seq)-based analysis revealed that these effects were mediated primarily by small changes in expression of indirect miR-9 targets rather than large changes in direct miR-9 targets; these indirect targets are enriched for migration-associated genes. Together, these data indicate that aberrant levels and activity of miR-9 may be one of the many factors that contribute to SZ risk, at least in a subset of patients.
| S-EPMC4856588 | biostudies-literature
Project description:BackgroundThe discovery of neural precursor cells (NPCs) and the concomitant intensive research in the field offer regenerative medicine novel approaches, enabling it to tackle conditions, such as neurodegenerative diseases. Transplantation of NPCs is nowadays considered a cutting-edge treatment for these conditions and many related clinical trials have been already completed or are still ongoing. However, little is known about the antigenicity of NPCs, with most studies addressing the question whether their antigenicity could lead to rejection of the transplanted cells.ResultsIn this study we investigated the antigenic potential of syngeneic NPCs emulsion, upon subcutaneous (s.c.) administration to wild type C57BL/6 mice, following a standard immunization protocol. The whole IgG repertoire expressed upon immunization was cloned into a Fab phage display vector. From the created phage display library, Fab expressing clones interacting with NPCs lysate proteins were selected with the biopanning technique. The IgG Fab fragment from clone 65 proved to be reactive against antigens originating from NPCs lysates and/or whole brain lysate in diverse immunological assays.ConclusionsUsing a standard immunization protocol to administer NPCs antigens, and applying the Fab fragment phage display technique, we were able to isolate at least a monoclonal IgG Fab fragment, which interacts with different mouse brain proteins. It is not clear whether such antibodies are produced in the host organisms, following NPCs transplantation.
| S-EPMC7398072 | biostudies-literature
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
2012-07-22 | GSE30912 | GEO