Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1188731 | ENA |
REPOSITORIES: ENA
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Project description:Tumors are composed of cellular subpopulations with varying degree of proliferative and tumorigenic potential. Here, we identify inter- and intra-tumor heterogeneous expression of histone variant H2AFV in numerous cancer types, with high H2AFV expression correlating with cancer stem cells, poorly differentiated tumors and inferior patient survival. Depletion of H2AFV impairs proliferation, invasiveness, tumorigenicity and tumor initiating cell frequency of glioblastoma. Mechanistically, H2AFV regulates chromatin accessibility of both active and repressive complexes at the promoters and enhancers of genes: the former activates genes involved in cell proliferation/self-renewal and invasiveness while the latter suppresses cellular differentiation in cancer stem cells. Our studies uncover H2AFV as an important epigenetic determinant in cancer stem cell fate and a significant contributor of intratumor heterogeneity.
2022-01-15 | GSE152858 | GEO
Project description:Tumors are composed of cellular subpopulations with varying degree of proliferative and tumorigenic potential. Here, we identify inter- and intra-tumor heterogeneous expression of histone variant H2AFV in numerous cancer types, with high H2AFV expression correlating with cancer stem cells, poorly differentiated tumors and inferior patient survival. Depletion of H2AFV impairs proliferation, invasiveness, tumorigenicity and tumor initiating cell frequency of glioblastoma. Mechanistically, H2AFV regulates chromatin accessibility of both active and repressive complexes at the promoters and enhancers of genes: the former activates genes involved in cell proliferation/self-renewal and invasiveness while the latter suppresses cellular differentiation in cancer stem cells. Our studies uncover H2AFV as an important epigenetic determinant in cancer stem cell fate and a significant contributor of intratumor heterogeneity.
2022-01-15 | GSE152861 | GEO
Project description:Kruppel-like factor-9 (KLF9), a member of the large KLF transcription factor family, has emerged as a regulator of oncogenesis, cell differentiation and neural development; however, the molecular basis for KLF9M-bM-^@M-^Ys diverse contextual functions remains unclear. This study focuses on the functions of KLF9 in human glioblastoma stem-like cells. We establish for the first time a genome-wide map of KLF9-regulated targets in human glioblastoma stem-like cells, and show that KLF9 functions as a transcriptional repressor and thereby regulates multiple signaling pathways involved in oncogenesis and stem cell regulation. A detailed analysis of one such pathway, integrin signaling, shows that the capacity of KLF9 to inhibit glioblastoma cell stemness and tumorigenicity requires ITGA6 repression. These findings enhance our understanding of the transcriptional networks underlying cancer cell stemness and differentiation, and identify KLF9-regulated molecular targets applicable to cancer therapeutics. Two cell lines were used as biological replicates. Each cell line have one KLF9 ChIP-enriched DNA sample and one input genomic DNA sample.
2014-10-10 | E-GEOD-62211 | biostudies-arrayexpress
Project description:The paper describes a model of glioblastoma.
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This model is described in the article:
Modeling the Treatment of Glioblastoma Multiforme and Cancer Stem Cells with Ordinary Differential Equations
Kristen Abernathy and Jeremy Burke BMC
Computational and Mathematical Methods in Medicine Volume 2016, Article ID 1239861, 11 pages
Abstract:
Despite improvements in cancer therapy and treatments, tumor recurrence is a common event in cancer patients. One explanation of recurrence is that cancer therapy focuses on treatment of tumor cells and does not eradicate cancer stem cells (CSCs). CSCs are postulated to behave similar to normal stem cells in that their role is to maintain homeostasis. That is, when the population of tumor cells is reduced or depleted by treatment, CSCs will repopulate the tumor, causing recurrence. In this paper, we study the application of the CSC Hypothesis to the treatment of glioblastoma multiforme by immunotherapy. We extend the work of Kogan et al. (2008) to incorporate the dynamics of CSCs, prove the existence of a recurrence state, and provide an analysis of possible cancerous states and their dependence on treatment levels.
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2024-09-02 | BIOMD0000000757 | BioModels
Project description:Glioblastomas are the most common malignant brain tumours in adults; they are highly aggressive, heterogeneous and plastic. We have identified METTL7B as an essential regulator of lineage specification in glioblastoma, with impact on both tumour size and invasiveness in in vivo models. Single cell transcriptomic analysis of these tumours and of cerebral organoids derived from expanded potential stem cells overexpressing METTL7B identified a regulatory role for the gene in the neural stem cells to astrocyte differentiation trajectory. Mechanistically, METTL7B downregulates the expression of key neuronal differentiation players, including SALL2, via DNA methylation and post-translational modifications of histone marks.
2024-07-01 | GSE242326 | GEO
Project description:Background: Prion diseases such as bovine spongiform encephalopathies (BSE) are transmissible neurodegenerative diseases which are presumably caused by an infectious conformational isoform of the cellular prion protein. Previous work has provided evidence that in murine prion disease the endogenous retrovirus (ERV) expression is altered in the brain. To determine if prion-induced changes in ERV expression are a general phenomenon we used a non-human primate model for prion disease. Results: Cynomolgus macaques (Macaca fasicularis) were infected intracerebrally with BSE-positive brain stem material from cattle and allowed to develop prion disease. Brain tissue from the basis pontis and vermis cerebelli of the six animals and the same regions from four healthy controls were subjected to ERV expression profiling using a retrovirus-specific microarray and quantitative real-time PCR. We could show that Class I gammaretroviruses HERV-E4-1, ERV-9, and MacERV-4 increase expression in BSE-infected macaques. In a second approach, we analysed ERV-K-(HML-2) RNA and protein expression in extracts from the same cynomolgus macaques. Here we found a significant downregulation of both, the macaque ERV-K-(HML-2) Gag protein and RNA in the frontal/parietal cortex of BSE-infected macaques. Conclusions: We provide evidence that dysregulation of ERVs in response to BSE-infection can be detected on both, the RNA and the protein level. To our knowledge, this is the first report on the differential expression of ERV-derived structural proteins in prion disorders. Our findings suggest that endogenous retroviruses may induce or exacerbate the pathological consequences of prion-associated neurodegeneration. Cynomolgus macaques (Macaca fasicularis) were infected intracerebrally with BSE-positive brain stem material from cattle and allowed to develop prion disease. Brain tissue from the basis pontis and vermis cerebelli of the six animals and the same regions from four healthy controls were subjected to ERV expression profiling using a retrovirus-specific microarray and quantitative real-time PCR. In a second approach, ERV-K-(HML-2) RNA and protein expression was analysed in extracts from the same cynomolgus macaques.
2011-06-10 | E-GEOD-29818 | biostudies-arrayexpress
Project description:Glioblastomas are the most lethal tumors affecting the central nervous system in adults. Simple and inexpensive syngeneic in vivo models that closely mirror human glioblastoma, including interactions between tumor and immune cells, are urgently needed for deciphering glioma biology and developing more effective treatments. Here, we generated mouse glioblastoma cell lines by repeated in-vivo passaging of neural stem cells and tumor tissue of a neural stem cell-specific Pten/p53 double-knockout genetic mouse model. Transcriptome and genome analyses of the cell lines revealed molecular heterogeneity comparable to that observed in human glioblastoma. Upon orthotopic transplantation into syngeneic hosts they formed high-grade gliomas that faithfully recapitulated the histopathological characteristics, invasiveness and infiltration by myeloid cells characteristic of human glioblastoma. These features make our cell lines unique and useful tools to study multiple aspects of glioma pathomechanism and test immunotherapies in syngeneic preclinical models.
2021-01-27 | GSE145558 | GEO
Project description:Glioblastomas are the most lethal tumors affecting the central nervous system in adults. Simple and inexpensive syngeneic in vivo models that closely mirror human glioblastoma, including interactions between tumor and immune cells, are urgently needed for deciphering glioma biology and developing more effective treatments. Here, we generated mouse glioblastoma cell lines by repeated in-vivo passaging of neural stem cells and tumor tissue of a neural stem cell-specific Pten/p53 double-knockout genetic mouse model. Transcriptome and genome analyses of the cell lines revealed molecular heterogeneity comparable to that observed in human glioblastoma. Upon orthotopic transplantation into syngeneic hosts they formed high-grade gliomas that faithfully recapitulated the histopathological characteristics, invasiveness and infiltration by myeloid cells characteristic of human glioblastoma. These features make our cell lines unique and useful tools to study multiple aspects of glioma pathomechanism and test immunotherapies in syngeneic preclinical models.
2021-01-27 | GSE145557 | GEO
Project description:This report describes our study of the efficacy and the potential mechanism underlying the anti-prion action of a new anti-prion compound having a glycoside structure in prion-infected cells. The study revealed involvements of two factors in the mechanism of the compound action: interferon and a microtubule nucleation activator, phosphodiesterase 4D interacting protein. In particular, phosphodiesterase 4D interacting protein was suggested to be important in regulating the trafficking or fusion of prion protein-containing vesicles or structures in cells. The findings of the study are expected to be useful not only for the elucidation of cellular regulatory mechanisms of prion protein, but also for the implication of new targets for therapeutic development. Prion-infected N167 cells were treated with either anti-prion glycoside compound (Gly-9) or control glycoside compound (Gly-14) at a dose of 5 M-NM-<g/mL for three days. Then, gene expression profiles were analyzed by DNA microarray analysis. Experiments were performed in quadruplicate.
2014-02-22 | E-GEOD-55241 | biostudies-arrayexpress