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Organizational principles in glioblastoma: decoded by ptalign and targeted via SFRP1 [GBM]

ABSTRACT: Organizational principles in glioblastoma: decoded by ptalign and targeted via SFRP1 [GBM]

PROVIDER: PRJNA1004603 | ENA |

REPOSITORIES: ENA

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Organizational principles in glioblastoma: decoded by ptalign and targeted via SFRP1

Project description:Organizational principles in glioblastoma: decoded by ptalign and targeted via SFRP1

| PRJNA1004600 | ENA

Organizational principles in glioblastoma: decoded by ptalign and targeted via SFRP1 [GBM]

Project description:Cancer research has largely focused on understanding mutations driving uncontrolled growth, leaving the organization of cellular hierarchies that sustain tumor progression less explored. We address this gap with ptalign, a tool that decodes such hierarchies in glioblastoma. By introducing the concept of pseudolineages mirroring adult neural stem cell lineages, we establish a correspondence between tumor pseudolineage and patient survival, devising biomarkers enabling cost-effective pseudolineage-based patient stratification. Comparing tumor pseudolineages to adult neural stem cell lineages, we identify the recurrent loss of the secreted Wnt antagonist SFRP1 in glioblastoma. This Wnt antagonist is expressed after the transition from dormant to quiescent neural stem cells, regulating their activation. Introducing SFRP1 into glioblastoma induced the generation of dormant astrocyte-like tumor cells, thereby increasing the quiescent tumor cell fraction and suggesting its potential as a target to arrest tumor progression. The insights facilitated by ptalign offer a new perspective on glioblastoma's cellular organization, providing a framework for understanding and treating glioblastomas and other solid tumors.

2023-12-01 | GSE240675 | GEO

Genetically defined human GBM organoids reveal principles of GBM development and actionable targets

Project description:Genetically defined human GBM organoids reveal principles of GBM development and actionable targets

| PRJNA882668 | ENA

Organizational principles in glioblastoma: decoded by ptalign and targeted via SFRP1

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-12-01 | GSE240676 | GEO

Genetically defined human GBM organoids reveal principles of GBM development and actionable targets

Project description:Recent advances in glioblastoma (GBM) studies provide a comprehensive catalog of its genetic aberrations and cellular heterogeneity. However, a solid understanding of genotype-based analysis of cancer pathway dependency and actionable target identification is required to transform GBM treatment into a personalized era. Here, we generated a spectrum of mutant iPSCs harboring frequent GBM mutations with CRISPR/Cas9 and profiled the organoids (LEGO: Laboratory Engineered Glioblastoma Organoid) derived from these iPSCs temporally on transcriptome, methylome, metabolome, lipidome, proteome, and phospho-proteome levels. We found that LEGOs form brain tumors in vivo and recapitulate critical features of human GBM. The multi-omics analysis discovered essential milestones driven by genetic heterogeneity during GBM progressions, such as lineage alteration, methylome rewriting, and metabolome/lipidome reprogramming, in concordance with altered pathway activity and drug response. This study provides a tool and research path to realizing genome-based personalized GBM therapy using novel advanced models.

2022-09-17 | ST002284 | MetabolomicsWorkbench

Proteogenomic anlalysis of glioblastoma (GBM)

Project description:Proteogenomic anlalysis of glioblastoma (GBM)

| PRJNA627121 | ENA

In vitro models of glioblastoma (GBM)

Project description:Characterization of gene expression for a panel of 50 in vitro and in vivo models of glioblastoma (GBM). Models include subcutaneously established xenograft lines, orthotopically grown subcutaneously established xenograft lines, serum derived cell lines and stem cell media derived cell lines. Multiple replicates of each line were run on different dates to determine the effect of batch and processing date on reproducibility of gene expression profiles 117 samples analyzed from 50 distinct GBM xenografts or cell lines. Biological replicates from the same passage number were included for many, but not all, of the lines.

2011-12-01 | E-GEOD-26344 | biostudies-arrayexpress

RNA-seq of human glioblastoma (GBM) cell lines treated with shRNA against GJB2, SCN9A, or non-targeted controls

Project description:Ion channels and related proteins of the ion permeome (IP) are common drug targets; however, their roles in cancer remain understudied. We performed a computational, pan-cancer analysis of druggable IP genes to prioritise targets for therapeutic and biomarker development. Two candidate biomarkers in glioblastoma (GBM), GJB2 and SCN9A, associated with poor prognosis in multiple datasets, as well as inter- and intratumoral heterogeneity and malignant cell types. We used shRNA to knock down GJB2 (G5) and SCN9A (S3) in patient-derived GBM cells (729) in triplicates and performed whole transcriptome sequencing to profile the transcriptome-wide changes. Pathway enrichment identified neural projection and proliferation pathways were significantly dysregulated in GJB2 and SCN9A GBM cell line knockdowns compared to non-targeted shRNA controls (Scr). Our study underlines altered bioelectrical signalling as a cancer hallmark and provides a catalogue of IP genes for functional experiments and therapy development.

2023-09-29 | E-MTAB-12859 | biostudies-arrayexpress

Genome-wide methylation analyses in glioblastoma multiforme (GBM)

Project description:Our main objective was to study genome-wide differential methylation in de novo glioblastoma multiforme (GBM, grade IV glioma). We evaluated CpG sites in gene promoters of 26,000+ genes using an array-based chip. We retrieved 54 GBM from biorepositories of two institutions(40 from Columbia University and 14 from Case Western Reserve University) and 24 control brain tissues from the New York Brain Bank, which collected control brain tissues from consented subjects without history of neurological diseases at autopsy. Bisulfite modified DNA was extracted from 54 GBM and 24 control brain tissue. The HumanMethylation27 Analysis Bead-Chips (Illumina) were used to interrogate 26,486 informative CpG sites in the autosomes.

2013-10-18 | E-GEOD-50923 | biostudies-arrayexpress

Gene expression in glioblastoma (GBM) tissues, glioblastoma stem-like cell (GSC) cultures and neural foetal cell line (NFC)

Project description:This microarray contains expression data for two GBM tissue samples, four GSC cultures grown as spheres and one NFC culture grown as spheres Total RNA was isolated from GSC cultures and GBM tissues

2015-11-26 | E-GEOD-60705 | biostudies-arrayexpress

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