Project description:Glioblastoma multiforme (GBM) presents a formidable clinical challenge due to its complex microenvironment. Here, we introduce lipid droplet (LD)-loaded macrophages, or tumor-associated foam cells (TAFs), as a previously unidentified immune cell population 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 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. Disruptin
Project description:Experiment description to give context to the data set: Ductal carcinoma in situ (DCIS), the most common type of pre-invasive lesion of breast, is being detected with increasing frequency with the advent of mammographic screening. Surgery is the mainstay for the treatment of DCIS. Based on the clinic-pathological features of DCIS, this may be followed by radiotherapy and/or endocrine therapy. The qualitative assessment of histological grade, expression of single protein biomarkers and more recently, mRNA analysis (DCIS Score) have been used to make these decisions. However, these factors do not fully predict the likelihood of development of invasive breast cancer treated with breast-conserving surgery. A majority of women with ductal carcinoma in situ (DCIS) receive breast-conserving surgery (BCS) but then face a risk of development of invasive breast cancer. Using Human Clariom D Pico Assay, we aim to compare the transcriptome profiles of DCIS in relation to development of invasive breast cancer (INV-BC) versus Non-INV-BC cases. Experimental Methods Clariom D Pico Human Transcriptome Array were performed according to Applied Biosystems/Thermo Fisher Scientific’s instructions. Experimental protocols are summarized in detail in Supplementary Methods (Supplementary Data). Sample annotation We compared the relative gene expression in development of invasive breast cancer (INV-BC) versus Non-INV-BC cases in Singapore cohort-59 cases (discovery cohort) and Italian cohort-50 cases (validation cohort). Microplate Plate and Well IDs are also provided as Clariom D ID list per cohort. Author information Dr. Sunil Badve is the Principal Investigator. Raw Data Probe Cell Intensity (CELL) and .ARR files which contain the design information for this study are provided (Human Clariom D Pico Assay).
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:Differential gene expression between groups of homogenous cell types is a biological question whose time has come. RNA can be extracted from small numbers of cells, such as those isolated by laser capture microdissection, but the small amounts obtained often require amplification to enable whole genome transcriptome profiling by technologies such as microarray analysis and RNA-seq. Recently, advances in amplification procedures make amplification directly from whole cell lysates possible. The aim of this study was to compare two amplification systems for variations in observed RNA abundance attributable to the amplification procedure for use with small quantities of cells isolated by laser capture microdissection. Arabidopsis root cells undergoing giant cell formation due to nematode infestation and un-infested control root cells were laser captured and used to evaluate 2 amplification systems. One, NuGEN's WT-Ovation Pico amplification system, uses total RNA as starting material while the other, NuGEN's WT-One-Direct Amplification system, uses lysate containing the captured cells. The reproducibility of whole genome transcript profiling and correlations of both systems were investigated after microarray analysis. The NuGEN WT-Ovation One-Direct system was less reproducible and more variable than the NuGEN WT-Ovation Pico system. The NuGEN WT-Ovation Pico Amplification kit resulted in the detection of thousands of genes differentially expressed genes between giant cells and control cells. This is in marked contrast to the relatively few genes detected after amplification with the NuGEN WT-Ovation One-Direct Amplification kit.