Similar Datasets
Project description:The recent identification of cancer stem cells (CSCs) in multiple human cancers provides a new inroad to understanding tumorigenesis at the cellular level. CSCs are defined by their characteristics of self-renewal, multipotentiality, and tumor initiation upon transplantation. By testing for these defining characteristics, we provide evidence for the existence of CSCs in a transgenic mouse model of glioma, S100Ã-verbB;Trp53. In this glioma model, CSCs are enriched in the side-population (SP) cells. These SP cells have enhanced tumor-initiating capacity, self-renewal, and multipotentiality compared to non-SP cells from the same tumors. Furthermore, gene expression analysis comparing FACS-sorted cancer SP cells to non-SP cancer cells and normal neural SP cells identified 45 candidate genes that are differentially expressed in glioma stem cells. We validated the expression of two genes from this list (S100a4 and S100a6) in primary mouse gliomas and human glioma samples. Analyses of xenografted human GBM (glioblatoma multiforme) cell lines and primary human glioma tissues show that S100A4 and S100A6 are expressed in a small subset of cancer cells and that their abundance is positively correlated to tumor grade. In conclusion, this study shows that CSCs exist in a mouse glioma model, suggesting that this model can be used to study the molecular and cellular characteristics of CSCs in vivo and to further test the cancer stem cell hypothesis. Experiment Overall Design: This study features two factors, injected cell origin (either tumorsphere or neurosphere) and FACS cell population (either side population or non-side population cells). There were two different tumorspheres, labeled 3447 and 4346 that were isolated from brain tumors in S100beta-verbB;p53-/- or S100beta-verbB;p53+/- mice. The tumorspheres were injected separately into the brains of NOD.Cg-Prkdc<scid>Il2rg<tm1Wjl>/SzJ mice to generate biological triplicates of each primary tumor. Tumorspheres were isolated and cultured before FACS sorting to obtain side population and non-side population cells. As a control, untransformed neurospheres from three independent S100beta-verbB;p53-/- or S100beta-verbB;p53+/- mice were isolated, cultured, and FACS sorted to obtain side population and non-side population cells. Side population and non-side population cells cultured from three mice injected with the 3447 cultured tumorspheres were assayed for gene expression (six samples). Side-population stem cells cultured from three mice injected with the 4346 cultured tumorspheres were assayed for gene expression (three samples). Side-population and non-side population cells cultured from three mice injected with the neurospheres were assayed for gene expression (six samples).
2009-01-13 | E-GEOD-13490 | biostudies-arrayexpress
Project description:Glioblastoma (GBM) is among the most aggressive cancers. Despite aggressive radiotherapy and treatment with the alkylating agent temozolomide (TMZ), patients ultimately succumb to the disease. Although much interest has focused on highly tumorigenic GBM stem cells (GSCs), adaption of a concept from microbial research proposes that a minor population of dormant âpersisterâ cells in cancer evade current therapies. To separate dormant and treatment-resistant tumor cells in human GBM tumorspheres, we have refined density gradient protocols previously used for separation of neurosphere-forming neural stem cells (NSCs). We find that a minor cell population in human GBM tumorsphere cultures and patient-derived tumor biopsies display increased cell density. These high-density GBM cells (HDGCs) display dormancy, variable expression of proposed GSC markers, and 10-100 fold higher levels of reprogramming gene expression compared to low-density GBM cells (LDGCs). Transcriptional profiling data confirmed the slow-cycling state of HDGCs. As a result, HDGCs show decreased tumorsphere formation capacity in vitro and reduced tumorigenicity in vivo. Using tumorspheres and xenografts, we demonstrated that HDGCs show increased treatment-resistance to ionizing radiation (IR) and temozolomide treatment compared to LDGCs. Similar to the NSC lineage, our data suggest that dormant HDGCs become increasingly sensitive to anti-proliferative therapies as they become activated and further differentiate. In conclusion, density gradients represents a marker-independent approach to separate dormant and treatment-resistant tumor cells in human GBMs and other solid cancers. 12 samples, no replicates, derived from 5 individual patients
2016-07-01 | E-GEOD-71116 | biostudies-arrayexpress
Project description:High-throughput sequencing of transcript tags from normal and glioblastoma-derived neural stem cell lines
2012-09-21 | E-MTAB-971 | biostudies-arrayexpress
Project description:To determine which signalling pathways are affected by small RNAs (piRNAs, miRNAs) through target regulation in Glioblastoma Multiforme (GBM), we performed high-throughput next-generation sequencing in U87-MG GBM cell line. The RNA sequencing (RNA-Seq) of small RNAs and transcriptomes discovered both known and novel piRNAs and miRNAs as well other transcriptomes of protein-coding genes, lncRNAs and pseudogenes expressed in this GBM cell line. These small RNAs and target transcriptomes can be further investigated to decode novel molecular mechanisms underlying oncogenesis of this malignancy.
2023-04-04 | GSE197508 | GEO
Project description:We established tumorspheres from human glioblastoma U87MG cells by single cell-derived tumorsphere formation. Among these tumorspheres, P4E8 clone showed cancer stem cell like properties such as self-renewal capacity, expression of cancer stem cell markers, resistance to anti-cancer agents and in vivo tumorigenicity. To find novel therapeutic target molecules, we performed differential gene expression analysis between U87MG and P4E8 cells.
2021-06-10 | GSE146698 | GEO
Project description:We report the application of Single-Cell RNA-Sequencing technology for high-throughput profiling in human primary HCC tumorspheres. By obtaining human primary HCC cells isolated from tumor tissues of PDX mice, we proceeded sphere-forming culture and then performed Single-Cell RNA-Sequencing of human primary HCC cells. The scRNA-Seq libraries were prepared with Single Cell 3′ Reagent Kit v2 (10×Genomics) following the user guide provided. We found that SCARB2 positive cells accounted about 11.3% of total tumorspheres and were enriched with MYC target genes. We conclude that Single-Cell RNA-Sequencing would expedite genetic network analyses and permit the dissection of complex biologic functions.
2023-08-11 | GSE185839 | GEO
Project description:Glioblastoma (GBM) is among the most aggressive cancers. Despite aggressive radiotherapy and treatment with the alkylating agent temozolomide (TMZ), patients ultimately succumb to the disease. Although much interest has focused on highly tumorigenic GBM stem cells (GSCs), adaption of a concept from microbial research proposes that a minor population of dormant “persister” cells in cancer evade current therapies. To separate dormant and treatment-resistant tumor cells in human GBM tumorspheres, we have refined density gradient protocols previously used for separation of neurosphere-forming neural stem cells (NSCs). We find that a minor cell population in human GBM tumorsphere cultures and patient-derived tumor biopsies display increased cell density. These high-density GBM cells (HDGCs) display dormancy, variable expression of proposed GSC markers, and 10-100 fold higher levels of reprogramming gene expression compared to low-density GBM cells (LDGCs). Transcriptional profiling data confirmed the slow-cycling state of HDGCs. As a result, HDGCs show decreased tumorsphere formation capacity in vitro and reduced tumorigenicity in vivo. Using tumorspheres and xenografts, we demonstrated that HDGCs show increased treatment-resistance to ionizing radiation (IR) and temozolomide treatment compared to LDGCs. Similar to the NSC lineage, our data suggest that dormant HDGCs become increasingly sensitive to anti-proliferative therapies as they become activated and further differentiate. In conclusion, density gradients represents a marker-independent approach to separate dormant and treatment-resistant tumor cells in human GBMs and other solid cancers.
2016-07-01 | GSE71116 | GEO
Project description:In this study, we employed high-throughput RNA sequencing (RNA-Seq) to identify the Smad3-dependent lncRNAs related to renal inflammation and fibrosis in Smad3 knockout (KO) mouse models of unilateral ureteral obstructive nephropathy (UUO) and immunologically-induced anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). 12 kidney tissue samples of Smad3 KO/WT mice from normal control, UUO at day 5 or anti-GBM GN at day 10 models (n=2 in each group) for whole transcriptome RNA-sequencing.
2014-03-26 | E-GEOD-55808 | biostudies-arrayexpress
Project description:Interventions: Case vs control:No
Primary outcome(s): High-throughput sequencing
Study Design: Case-Control study
| 2676067 | ecrin-mdr-crc
Project description:Malignant gliomas represent the most devastating group of brain tumors in adults, among which glioblastoma multiforme (GBM) exhibits the highest malignancy rate. Despite combined modality treatment, GBM recurs and is invariably fatal. A further insight into molecular background of gliomagenesis is required to improve patient outcome. The first aim of this study was to gain broad information on miRNA expression pattern in malignant gliomas, mainly GBM. We investigated the global miRNA profile of malignant glioma tissues by means of miRNA microarrays, deep sequencing and meta-analysis. We selected miRNAs the most frequently deregulated in glioblastoma tissues as well as peritumoral brain areas in comparison to normal human brain. We found candidate miRNAs contributing to progression from gliomas grade III to gliomas grade IV. The meta-analysis of miRNA profiling studies in GBM tissues summarizes the past and recent advances in an investigation of miRNA signature in GBM versus noncancerous human brain and provides a comprehensive overview. We proposed a set of 35 miRNAs which expression is the most frequently deregulated in GBM patients and 30 miRNA candidates recognized as novel GBM biomarkers. miRNA expression profile in the adult malignant gliomas, glioma peritumoral tissues and normal human brain.
2014-09-26 | E-GEOD-61710 | biostudies-arrayexpress