Integrative and Quantitative Analysis of Tumor Progression Reveals Fundamental Properties of Glioblastoma
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PROVIDER: PRJNA471501 | ENA |
REPOSITORIES: ENA
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Project description:Integrative and Quantitative Analysis of Tumor Progression Reveals Fundamental Properties of Glioblastoma
| PRJNA521323 | ENA
Project description:The principle of tumor growth is one of the most fundamental aspects in cancer biology and it remains to be superficially understood. Here we developed a set of genetic and mathematical tools for integrative analysis of mouse glioblastoma (GBM) progression. Quantitative temporal imaging of mouse GBM and mathematical modeling suggest that mouse GBM grows exponentially, which led to the discovery that a sustainable exponential growth requires outward migrating brain tumor stem cells (BTSCs). Quantitative single cell tracing of BTSCs in vivo unravels symmetric expansion of BTSCs, asymmetric differentiation, and a non-reversible differentiation process during tumor progression. Mosaic tracing of BTSCs and non-BTSCs reveals cellular dynamic changes and turnover. These experimentally collected parameters were integrated step by step to a quantitative mathematical model of GBM growth, which faithfully predicts tumor cellular architecture, tumor response to chemotherapy and BTSC therapy. Bulk and single cell RNA-Seq reveals distinct molecular hierarchy and molecular heterogeneity in BTSCs, which was confirmed by analyzing human GBM single-cell RNA-Seq results. This study reveals fundamental developmental principles that govern tumor growth, which provides insights into understanding cancer development, tumor heterogeneity and GBM therapy.
2022-02-02 | GSE126212 | GEO
Project description:Principle of tumor growth is one fundamental aspect of cancer biology and it remains to be superficially understood. Here we developed a set of genetic and mathematic tools allow integrative analysis of mouse glioblastoma (GBM) progression. Quantitative temporal imaging of mouse GBM and mathematic modeling suggest that mouse GBM grows exponentially, which led to the discovery that a sustainable exponential growth requires outward migrating brain tumor stem cells (BTSCs). Quantitative single cell tracing of BTSCs in vivo unravels symmetric expansion of BTSCs, asymmetric differentiation, and a non-reversible differentiation process during tumor progression. Mosaic tracing of BTSCs and non-BTSCs reveals a cellular temporal dynamic changes and cellular turnover. These experimentally collected parameters were integrated step by step to a quantitative mathematic model of GBM growth, which faithfully predicts tumor cellular architecture, tumor response to chemotherapy and BTSC therapy. Bulk and single cell RNA-Seq reveals distinct molecular hierarchy and molecular heterogeneity in BTSCs, which was confirmed by analyzing human GBM single cell RNA-Seq results. This study reveals basic developmental principles that govern tumor development, which provides novel understanding of cancer development, tumor heterogeneity and new approaches to treat GBM.
2024-05-01 | GSE114456 | GEO
Project description:Integrative spatial analysis reveals a multi-layered organization of glioblastoma
| PRJNA994130 | ENA
Project description:An integrative analysis of the SOX2 response program in glioblastoma
| PRJNA130651 | ENA
Project description:Glioblastoma is one of the most malignant brain tumors with poor prognosis and their development and progression are known to be driven by glioblastoma stem cells. Although glioblastoma stem cells lose their cancer stemness properties during cultivation in serum-containing medium, little is known about the molecular mechanisms regulating signaling alteration in relation to reduction of stemness. In order to elucidate the global phosphorylation-related signaling events, we performed a SILAC-based quantitative phosphoproteome analysis of serum-induced dynamics in glioblastoma stem cells established from the tumor tissues of the patient. Among a total of 2,876 phosphorylation sites on 1,584 proteins identified in our analysis, 732 phosphorylation sites on 419 proteins were regulated through the alteration of stem cell characteristics.
2016-01-13 | PXD002614 | Pride
Project description:Glioblastoma multiforme shows multiple chromosomal aberrations, the impact of which on gene expression remains unclear. To investigate this relationship and to identify putative initiating genomic events, we integrated a paired copy number and gene expression survey in glioblastoma using whole human genome arrays. Loci of recurrent copy number alterations were combined with gene expression profiles obtained on the same tumor samples. We identified a set of 406 ‘cis-acting DNA targeted genes’ corresponding to genomic aberrations with direct copy-number-driving changes in gene expression, defined as genes with either significantly concordant or correlated changes in DNA copy number and expression. Functional annotation revealed that these genes participate in key processes of cancer cell biology, providing insights into the genetic mechanisms driving glioblastoma. The robustness of the gene selection was validated on an external microarray data set including 81 glioblastomas and 23 non-neoplastic brain samples. The integration of array CGH and gene expression data highlights a robust ‘cis-acting DNA targeted genes’ signature that may be critical for glioblastoma progression, with two tumor suppressor genes PCDH9 and STARD13 that could be involved in tumor invasiveness and resistance to etoposide. Keywords: Glioblastoma Multiforme, array CGH, microarray, data integration
2008-10-30 | GSE10878 | GEO
Project description:Cancer stem cells are believed to be responsible for tumor initiation and development. Much current research on human brain tumors is focused on the stem-like properties of glioblastoma stem cells. Anaplastic lymphoma kinase (ALK) and its ligand pleiotrophin are required for maintaining the stem-like properties and tumorigenicity of glioblastoma stem cells. Human glioblastoma stem cells (GB2) were infected with a lentivirus expressing an shRNA targeting ALK or pleiotrophin.
2011-09-30 | E-GEOD-32482 | biostudies-arrayexpress
Project description:Large intergenic non-coding RNAs (lincRNAs) are emerging as key regulators of diverse cellular processes. Determining the function of individual lincRNAs remains a challenge. Recent advances in RNA sequencing (RNA-Seq) and computational methods allow for an unprecedented analysis of such transcripts. Here, we present an integrative approach to define a reference catalogue of over 8,000 human lincRNAs. Our catalogue unifies previously existing annotation sources with transcripts we assembled from RNA-Seq data collected from ~4 billion RNA-Seq reads across 24 tissues and cell types. We characterize each lincRNA by a panorama of more than 30 properties, including sequence, structural, transcriptional, and orthology features. We find that lincRNA expression is strikingly tissue specific compared to coding genes, and that they are typically co-expressed with their neighboring genes, albeit to a similar extent to that of pairs of neighboring protein-coding genes. We distinguish an additional sub-set of transcripts that have high evolutionary conservation but may include short open reading frames, and may serve either as lincRNAs or as small peptides. Our integrated, comprehensive, yet conservative reference catalogue of human lincRNAs reveals the global properties of lincRNAs and will facilitate experimental studies and further functional classification of these genes. We extracted profiled the transcriptome expression polyadenylated mRNA-Seq. We then used these to reconstruct the transcriptome using de-novo assemblers and identify long non coding RNAs and their expression.
2011-08-27 | E-GEOD-30554 | biostudies-arrayexpress
Project description:We over-expressed an epigenetic regulator in a glioblastoma (GBM) primary culture from an adult patient. These GBM cells have cancer stem cell phenotypes, as they have self-renewal properties and tumor initiation potential when transplanted in immunocompromised mice. ATAC-seq was performed on cells over-expressing the epigenetic regulator and control cells expressing EGFP. ATAC-Seq on glioblastoma cells that over-express EGFP or an epigenetic regulator.
2015-12-08 | E-GEOD-67633 | biostudies-arrayexpress