Project description:Glioblastoma (GBM) presents a formidable clinical challenge due to its complex microenvironment. Here, we introduce tumor-associated foam cells (TAFs), a previously unidentified immune cell entity of lipid droplet (LD)-loaded macrophages, in GBM. Through extensive analyses of patient tumors, together with in vitro and in vivo investigations, we reveal that TAFs exhibit distinct pro-tumorigenic characteristics related to hypoxia, mesenchymal transition, angiogenesis, and impaired phagocytosis. Moreover, TAF presence correlates with worse patient outcome. Our mechanistic investigations demonstrate that TAF formation is facilitated by lipid cargo transfer from extracellular vesicles released by GBM cells. Importantly, we demonstrate that targeting key enzymes involved in LD formation, such as DGAT1 or ACSL, effectively disrupts TAF functionality. This study establishes TAFs as a prominent immune cell entity in GBM and provides valuable insights into their interplay within the microenvironment. Disrupting LD formation to target TAFs presents an interesting avenue for future therapeutic development in GBM.
Project description:This SuperSeries is composed of the following subset Series: GSE24446: Genetic abnormalities in GBM brain tumors GSE24452: Genetic abnormalities in various cell subpopulations of GBM brain tumors GSE24557: Exon-level expression profiles of GBM brain tumors Refer to individual Series
Project description:Human Glioblastoma Multiforme tumors taken before dendritic cell vaccination, the recurrent tumors taken after vaccination and control GBM tumors from non vaccinated patients. Experiment Overall Design: Six Glioblastoma Multiforme patients underwent surgery. Their brain tumors were removed and analyzed via microarray. The lysate from the tumors were cultured with the patients' dendritic cells and the DCs were injected back into the patients. The patients GBMs returned and they underwent surgery a second time and those tumors were also analyzed via microarray. Tumors from the first and second GBM surgeries of 5 patients who did not receive DC vaccines are included as controls.
Project description:Glioblastoma (GBM) patient-derived orthotopic xenografts (PDOXs) were derived from organotypic spheroids obtained from patient tumor samples. To detect whether gene expression profiles of GBM patient tumors are retained in PDOXs, we performed genome-wide transcript analysis by human-specific microarrays . In parallel, we analyzed GBM cell cultures and corresponding intracranial xenografts from stem-like (NCH421k, NCH644) and adherent GBM cell lines (U87, U251). PDOXs show a better transcriptomic resemblance with patient tumors than other preclinical models. The major difference is largely explained by the depletion of human-derived non-malignant cells.
Project description:GBM is a heterogenous tumor. Based on membrane protein expression, the GBM single cell dissociates were seperated into different subfractions by FACS assay. The genomic aberration among each populations were compared by analysis of CGH data.
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.
Project description:GBM is a heterogenous tumor. Based on membrane protein expression, the GBM single cell dissociates were seperated into different subfractions by FACS assay. The genomic aberration among each populations were compared by analysis of CGH data. Genomic DNA were extracted from sorted cell population and CGH assay were performed to compare the similarity genomic abnormality among different cell groups.
