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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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ST3GAL1-Associated Transcriptomic Program in Glioblastoma Tumor Growth, Invasion, and Prognosis

ABSTRACT: Cell surface sialylation confers many roles in cancer biology including cell proliferation, invasiveness, metastasis and angiogenesis. We show here that ST3Gal1 sialyltransferase marks a self-renewing cellular fraction. Depletion of ST3GAL1 abrogates glioma cell growth and tumorigenicity. In contrast, TGFb induces ST3GAL1 expression and correlates with the pattern of ST3Gal1 activation in patient tumors of the mesenchymal molecular subtype. To delineate the downstream events of ST3Gal1 signaling, we utilized a bioinformatical approach that leveraged on the greater statistical power of large patient databases, and subsequently verified our predictions in patient-derived glioma cells. We identify FoxM1, a major stem cell regulatory gene, as a downstream effector, and show that ST3Gal1 mediates the glioma phenotype through control of FoxM1 protein degradation Total RNA from primary neurosphere culture of brain tumor specimens non-treated and ST3GAL1 KD clones. The mRNAs of 5 unique glioma propagating cells (GPCs) were hybridized on Affymetrix HG-U133 Plus2 chips to study the transcriptomic impact of ST3GAL1 knock-down. Specimens were obtained from 5 glioma patients and replicate arrays were performed for all 5 neurosphere cultures.

ORGANISM(S): Homo sapiens

SUBMITTER: Edwin Sandanaraj

PROVIDER: E-GEOD-51395 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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ST3GAL1-Associated Transcriptomic Program in Glioblastoma Tumor Growth, Invasion, and Prognosis

Project description:Cell surface sialylation confers many roles in cancer biology including cell proliferation, invasiveness, metastasis and angiogenesis. We show here that ST3Gal1 sialyltransferase marks a self-renewing cellular fraction. Depletion of ST3GAL1 abrogates glioma cell growth and tumorigenicity. In contrast, TGFb induces ST3GAL1 expression and correlates with the pattern of ST3Gal1 activation in patient tumors of the mesenchymal molecular subtype. To delineate the downstream events of ST3Gal1 signaling, we utilized a bioinformatical approach that leveraged on the greater statistical power of large patient databases, and subsequently verified our predictions in patient-derived glioma cells. We identify FoxM1, a major stem cell regulatory gene, as a downstream effector, and show that ST3Gal1 mediates the glioma phenotype through control of FoxM1 protein degradation Total RNA from primary neurosphere culture of brain tumor specimens were flow-sorted to identify Peanut Agglutinin(PNA) affinity. The fractions of different degress of PNA bound GPCs were hybridized on Illumina Human Ref-8v2 bead chips to study the impact of transcriptome pattern of PNA affinity. Specimens were obtained from 4 patients and replicate arrays were performed for all 4 neurosphere cultures.

2015-11-09 | E-GEOD-51411 | biostudies-arrayexpress

Glioma-propagating cells as an in vitro screening platform: PLK1 as a case study

Project description:Gliomas are the most devastating of primary adult malignant brain tumors. These tumors are highly infiltrative and can arise from cells with extensive self-renewal capability and chemoresistance, frequently termed glioma-propagating cells (GPCs). GPCs are thus the plausible culprits of tumor recurrence. Treatment strategies that eradicate GPCs will greatly improve disease outcome. Such findings support the use of GPCs as in vitro cellular systems for small molecule screening. However, the nuances in utilizing GPCs as a cellular screening platform are not trivial. These slow-growing cells are typically cultured as suspension, spheroid structures in serum-free condition supplemented with growth factors. Consequently, replenishment of growth factors throughout the screening period must occur to maintain cells in their undifferentiated state, as the more lineage-committed, differentiated cells are less tumorigenic. We will present a case study of a small molecule screen conducted with GPCs and explain how unique sphere activity assays were implemented to distinguish drug efficacies against the long-term, self-renewing fraction, as opposed to transient-amplifying progenitors, latter of which are detected in conventional viability assays. We identified Pololike kinase 1 as a regulator of GPC survival. Finally, we leveraged on public glioma databases to illustrate GPC contribution to disease progression and patient survival outcome. Total RNA from primary neurosphere culture of brain tumor specimens were hybridized in baseline condition. Specimens were obtained from 11 patients and replicate arrays were performed for all 11 neurosphere cultures.

2012-08-01 | E-GEOD-36782 | biostudies-arrayexpress

ST3GAL1-Associated Transcriptomic Program in Glioblastoma Tumor Growth, Invasion, and Prognosis

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-11-07 | E-GEOD-51413 | biostudies-arrayexpress

Microarray analysis of U87 glioma cells after transient knockdown of FOXM1

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Gene Set Enrichment Analysis reveals lineage relationships between mouse and human gliomas and identifies stem cells and PNET as distinct entities

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2013-07-29 | E-GEOD-42515 | biostudies-arrayexpress

Gene expression profiling of neural stem cells derived from iPS cells (iPSc) of Sanfilippo syndrome type B (MPSIIIB) patient versus control

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ST3GAL1-Associated Transcriptomic Program in Glioblastoma Tumor Growth, Invasion, and Prognosis

2015-11-09 | GSE51411 | GEO

ST3GAL1-Associated Transcriptomic Program in Glioblastoma Tumor Growth, Invasion, and Prognosis

2015-11-09 | GSE51395 | GEO

Transcriptomic analysis of Bmi1 overexpression in NSPC.

Project description:We have previously shown that conditional overexpression of Bmi1 in NSC increases their proliferation both in the developing neocortexand in the postnatal brain (Yadirgi et al. 2011). However, during embryonic development, increased and ectopic proliferation induced by overexpression of Bmi1 in progenitors committed toward a neuronal lineage triggered apoptosis, leading eventually to a reduced overall brain size (Yadirgi et al. 2011). These findings M-bM-^@M-^Sincreased proliferation of neural stem/progenitor cells (NSPC) and apoptosis of neuronal committed progenitors - could be faithfully reproduced in an in vitro assay where NSPC isolated from Nestin-Cre; STOP FloxBmi1 embryos are cultured in floating conditions in the presence of EGF and FGF2 (neurosphere assay). We isolated NSPC from Nestin-Cre;STOP FloxBmi1 E16.5 neocortices and cultured them briefly under neurosphere inducing conditions. We then analysed their transcriptome by whole-genome Illumina platform mouse v2 and compared it to the transcriptome of NSPC isolated from non-transgenic or single transgenic littermates. The objective of this analysis was to identify genes differentially expressed upon overexpression of the PcG gene Bmi1 in neural stem/progenitor cells. 4 samples, 2 condition with 2 biological replicates per condition

2012-11-12 | E-GEOD-31607 | biostudies-arrayexpress

Comparison between mouse ES/iPS derived neurosphere and mouse primary culture of neurospheres obtained from fetal mouse ganglionic eminence

Project description:Recent reports have emphasized the pitfalls of iPSC technology including the potential for immunogenicity of transplanted cells. It is serious safety-related concern for iPSC-based cell therapy. However, preclinical data supporting the safety and efficacy of iPSCs are also accumulating. To address the concern of immunogenicity of ESCs/iPSCs or ESCs/iPSCs-derived neurospheres, global gene expression profiles were compared between undifferentiated mouse ESCs (EB3 line), mouse iPSCs (38C2 line), and ESC/iPSC-derived neurosphere and mouse primary culture of neurosphere obtained from fetal mouse ganglionic eminence. Mouse adult sklin fibroblast was used as a control. We used affymetrix microarrays to compare the global gene expression of neurospheres prepared several origins. Keywords: Expression profiling by array RNA extracted from neurospheres was hybridized to Affymetrix microarrays.

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