Epigenetic determinants of self-renewal in glioblastoma [ATAC-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE67633 | GEO | 2015/12/08
SECONDARY ACCESSION(S): PRJNA280596
REPOSITORIES: GEO
Similar Datasets
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
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. An epigenetic regulator (ER) was over-expressed in the GBM primary culture G514NS. EGFP was expressed from the same vector backbone as a control. N = 3 biological replicates for each of EGFP- and ER-overexpressing cells. Please note that complete data output (with 74,342 data rows) from Partek analysis contains several identifiers which are not represented in the GPL17586, and therefore is linked as Series supplementary file.
2015-11-11 | E-GEOD-63296 | biostudies-arrayexpress
Project description:Mutations in the histone 3 variant H3.3 have been identified in one-third of pediatric glioblastomas (GBMs), but not in adult tumors. Here we show that H3.3 is a dynamic determinant of functional properties in adult GBM. H3.3 is repressed by mixed lineage leukemia 5 (MLL5) in self-renewing GBM cells. MLL5 is a global epigenetic repressor that orchestrates reorganization of chromatin structure by punctuating chromosomes with foci of compacted chromatin, favoring tumorigenic and self-renewing properties. Conversely, H3.3 antagonizes self-renewal and promotes differentiation. We exploited these epigenetic states to rationally identify two small molecules that effectively curb cancer stem cell properties in a preclinical model. Our work uncovers a role for MLL5 and H3.3 in maintaining self-renewal hierarchies in adult GBM.
2015-11-11 | GSE63296 | GEO
Project description:Cytosine methylation is an epigenetic mark usually associated with gene repression. Despite a requirement for de novo DNA methylation for differentiation of embryonic stem cells, its role in somatic stem cells is unknown. Using conditional ablation, we show that loss of either, or both, Dnmt3a or Dnmt3b, progressively impedes hematopoietic stem cell (HSC) differentiation during serial in vivo passage. Concomitantly, HSC self-renewal is immensely augmented in absence of either Dnmt3, particularly Dnmt3a. Dnmt3-KO HSCs show upregulation of HSC multipotency genes and downregulation of early differentiation factors, and the differentiated progeny of Dnmt3-KO HSCs exhibit hypomethylation and incomplete repression of HSC-specific genes. HSCs lacking Dnmt3a manifest hyper-methylation of CpG islands and hypo-methylation of genes which are highly correlated with human hematologic malignancies. These data establish that aberrant DNA methylation has direct pathologic consequences for somatic stem cell development, leading to inefficient differentiation and maintenance of a self-renewal program. Reduced representation bisulfite sequencing (MspI,~40-220bp size fraction) of secondarily-transplanted wild-type and Dnmt3a conditional knockout hematopoietic stem cells. We used microarrays to detail the global expression of genes in secondarily-transplanted control-HSCs and Dnmt3a-KO-HSCs.
2011-09-30 | E-GEOD-27322 | biostudies-arrayexpress
Project description:Previously, we identified the transcription factor Zfx as a key regulator of self-renewal in murine ESCs. Here we extend those findings to human ESCs. Zfx knockdown in hESCs hindered clonal growth and decreased colony size after serial replating. Zfx overexpression enhanced clone formation, increased colony size and decreased expression of differentiation-related genes in human ESCs. Zfx-overexpressing hESCs resisted spontaneous differentiation but could be directed to differentiate into endodermal and neural cell fates when provided with the appropriate cues. Thus, Zfx acts as a molecular rheostat regulating the balance between self-renewal and differentiation in hESCs, revealing the close evolutionary conservation of the self-renewal mechanisms in murine and human ESCs. Human embryonic stem cells with over expression of ZFX were compared to the original cell line (H9) and a clonally derived wild-type cell line (clone 3)
2012-01-01 | E-GEOD-29784 | biostudies-arrayexpress
Project description:The embryonic stem (ES) cell transcriptional and epigenetic networks are critical for the maintenance of ES cell self-renewal. It remains unclear whether interactions. Here we show that a core member of the Set/MLL complex, WDrepeat protein-5 (Wdr5), is a novel regulator of self-renewal and partners with Oct4 to maintain an intact transcriptional network and for efficient formation of induced pluripotent stem (iPS) cells. Moreover, we provide evidence that Oct4 interacts with chromatin components and is indispensible for epigenetic regulation. These findings suggest an integrated transcriptional and epigenetic model, mediated through Wdr5, for the maintenance of ES cell self-renewal and somatic cell reprogramming. Differential gene expressions upon down-regulation of Wdr5 was analysed by comparing Wdr5R4 –dox (triplicate) and LucR +dox (duplicate) RNA samples Gene expression changes upon down-regulation of Oct4 was analysed by comparing Oct4 shRNA (duplicate) and GFP shRNA (duplicate) after 4day transfection Wdr5: 5 samples are analyzed: Luciferase (Luc, 2 replicates) and Wdr5 with no dox (minusDox, 3 replicates) Oct4-GFP: 4 samples are analyzed: Oct4 shRNA (Oct4, 2 replicates) and GFP shRNA (GFP, 2 replicates)
2011-04-08 | E-GEOD-19588 | biostudies-arrayexpress
Project description:The embryonic stem (ES) cell transcriptional and epigenetic networks are critical for the maintenance of ES cell self-renewal. However, it remains unclear whether components of these networks functionally interact and if so, what factors mediate such interactions. Here we show that WD-repeat protein-5 (Wdr5), a core member of the mammalian Trithorax (trxG) complex, positively correlates with the undifferentiated state and is a novel regulator of ES cell self-renewal. We demonstrate that Wdr5, an ‘effector’ of H3K4 methylation, interacts with the pluripotency transcription factor Oct4. In concordance, genome-wide ChIP-Seq and transcriptome analyses demonstrate overlapping gene regulatory functions between Oct4 and Wdr5. We show that the Oct4-Sox2-Nanog circuitry cooperates with trxG for transcriptional activation of key self-renewal regulators. Furthermore, Wdr5 expression is required for the efficient formation of induced pluripotent stem (iPS) cells. Collectively, these findings implicate an integrated model of transcriptional and epigenetic control, mediated by select trxG members, for the maintenance of ES cell self-renewal and somatic cell reprogramming. 7 Samples
2011-04-08 | E-GEOD-22934 | biostudies-arrayexpress
Project description:Deciphering the mechanisms that control the pluripotent ground state is key for understanding embryonic development. Nonetheless, the epigenetic regulation of ground-state mouse embryonic stem cells (mESCs) is not fully understood. Here, we identify the epigenetic protein MPP8 as being essential for ground-state pluripotency. Its depletion leads to cell cycle arrest and spontaneous differentiation. MPP8 has been suggested to repress LINE1 elements by recruiting the human silencing hub (HUSH) complex to H3K9me3-rich regions. Unexpectedly, we find that LINE1 elements are efficiently repressed by MPP8 lacking the chromodomain, while the unannotated C-terminus is essential for its function. Moreover, we show that SETDB1 recruits MPP8 to its genomic target loci, whereas transcriptional repression of LINE1 elements is maintained without retaining H3K9me3 levels. Taken together our findings demonstrate that MPP8 protects the DNA-hypomethylated pluripotent ground state through its association with the HUSH core complex, however, independently of detectable chromatin binding and maintenance of H3K9me3.
2021-03-21 | PXD019345 | Pride
Project description:Epigenetic control over IFN Type-I response antagonizes self-renewal in acute myeloid leukemia
| PRJNA871242 | ENA
Project description:Self-renewal is a crucial property of glioblastoma cells and is enabled by the choreographed function of chromatin regulators and transcription factors. Identifying targetable epigenetic mechanisms of self-renewal could represent an important step toward developing new and effective treatments for this universally lethal cancer. Here we uncover a targetable epigenetic axis of self-renewal mediated by the histone variant macroH2A2.
2023-02-15 | GSE212086 | GEO