Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA396764 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5888130_1.fastq.gz | Fastqsanger.gz | |||
| SRR5888130_2.fastq.gz | Fastqsanger.gz | |||
| SRR5888131_1.fastq.gz | Fastqsanger.gz | |||
| SRR5888131_2.fastq.gz | Fastqsanger.gz | |||
| SRR5888132_1.fastq.gz | Fastqsanger.gz |
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Project description:Glioblastoma (GBM) is a highly aggressive brain tumor, characterized by poorly differentiated cells that drive disease growth and relapse. In contrast to normal neural stem cells (NSCs) which show a highly orderly process of differentiation, GBM precursors exhibit differentiation failure. In order to identify new mechanisms involved in neuronal differentiation that may have bearing on understanding GBM, we performed an unbiased phenotypic screen, utilizing a library of mouse embryonic stem cell (mESC) clones carrying 1307 unique variable length haplodeletions (altogether covering 25% of the mouse genome). We identified a series of haplodeletions that conferred failed neuronal differentiation following neural lineage specification. Several hit clones contained a deletion on mouse chromosome 10, synteneic to human chromosome 10q, and included the Tet1 gene. Loss of a single allele of Tet1 was sufficient to confer the failed neuronal differentiation on mouse neural precursors by allowing stem cell programs to override early commitment steps leading to full reversion back to a stem cell state. By deleting TET1 in human GBM precursors, we show that loss of one allele of TET1 is sufficient to cause increased self renewal, decreased differentiation, and increased tumorigenicity, demonstrating TET1 to be a key target, along with PTEN, on 10q. Reduced TET1 dosage leads to global DNA hypermethylation and increased sensitivity to DNA methylation inhibitors, suggesting their application in a subset of GBMs.
2023-05-01 | GSE102136 | GEO
Project description:SUMMARY Terminal differentiation has been proposed as a therapeutic strategy for glioblastoma (GBM). Culturing of GBM derived tumor initiating glioma stem cells (GSCs) in fetal bovine serum containing media is a proposed mode of differentiation that is thought to induce loss of stem cell characteristics, promote neural lineage differentiation and a parallel loss of tumor initiation capacity. Here we show that GSCs retained both neurosphere formation and tumor initiation abilities after short or long term serum exposure. Under serum induced differentiating conditions, GSCs expressed both neural lineage and stem cell markers, highlighting the aberrant pseudo-differentiation state. GSCs maintained under adherent differentiating conditions continued to proliferate and initiate tumor formation with efficiencies similar to GSCs maintained under proliferating (neurosphere) conditions. Proneural (PN) GSCs under serum exposure showed an induction of mesenchymal (MES) gene expression signatures. Our data indicate that the tumor initiation ability of GSCs is independent of their differentiation state and that terminal differentiation as a therapeutic approach may not effectively negate tumorigenicity of GSCs. SIGNIFICANCE Terminal differentiation has been proposed as a therapeutic strategy for glioblastoma (GBM). Culturing of GBM derived tumor initiating glioma stem cells (GSCs) in fetal bovine serum containing media is a proposed mode of differentiation that is thought to induce loss of stem cell characteristics, promote neural lineage differentiation and a parallel loss of tumor initiation capacity. Here we show that GSCs retained both neurosphere formation and tumor initiation abilities after short or long term serum exposure. Under serum induced differentiating conditions, GSCs expressed both neural lineage and stem cell markers, highlighting the aberrant pseudo-differentiation state. GSCs maintained under adherent differentiating conditions continued to proliferate and initiate tumor formation with efficiencies similar to GSCs maintained under proliferating (neurosphere) conditions. Proneural (PN) GSCs under serum exposure showed an induction of mesenchymal (MES) gene expression signatures. Our data indicate that the tumor initiation ability of GSCs is independent of their differentiation state and that terminal differentiation as a therapeutic approach may not effectively negate tumorigenicity of GSCs.
2015-09-01 | GSE58922 | GEO
Project description:SUMMARY Terminal differentiation has been proposed as a therapeutic strategy for glioblastoma (GBM). Culturing of GBM derived tumor initiating glioma stem cells (GSCs) in fetal bovine serum containing media is a proposed mode of differentiation that is thought to induce loss of stem cell characteristics, promote neural lineage differentiation and a parallel loss of tumor initiation capacity. Here we show that GSCs retained both neurosphere formation and tumor initiation abilities after short or long term serum exposure. Under serum induced differentiating conditions, GSCs expressed both neural lineage and stem cell markers, highlighting the aberrant pseudo-differentiation state. GSCs maintained under adherent differentiating conditions continued to proliferate and initiate tumor formation with efficiencies similar to GSCs maintained under proliferating (neurosphere) conditions. Proneural (PN) GSCs under serum exposure showed an induction of mesenchymal (MES) gene expression signatures. Our data indicate that the tumor initiation ability of GSCs is independent of their differentiation state and that terminal differentiation as a therapeutic approach may not effectively negate tumorigenicity of GSCs. SIGNIFICANCE Terminal differentiation has been proposed as a therapeutic strategy for glioblastoma (GBM). Culturing of GBM derived tumor initiating glioma stem cells (GSCs) in fetal bovine serum containing media is a proposed mode of differentiation that is thought to induce loss of stem cell characteristics, promote neural lineage differentiation and a parallel loss of tumor initiation capacity. Here we show that GSCs retained both neurosphere formation and tumor initiation abilities after short or long term serum exposure. Under serum induced differentiating conditions, GSCs expressed both neural lineage and stem cell markers, highlighting the aberrant pseudo-differentiation state. GSCs maintained under adherent differentiating conditions continued to proliferate and initiate tumor formation with efficiencies similar to GSCs maintained under proliferating (neurosphere) conditions. Proneural (PN) GSCs under serum exposure showed an induction of mesenchymal (MES) gene expression signatures. Our data indicate that the tumor initiation ability of GSCs is independent of their differentiation state and that terminal differentiation as a therapeutic approach may not effectively negate tumorigenicity of GSCs.
2015-09-01 | GSE58921 | GEO
Project description:SUMMARY Terminal differentiation has been proposed as a therapeutic strategy for glioblastoma (GBM). Culturing of GBM derived tumor initiating glioma stem cells (GSCs) in fetal bovine serum containing media is a proposed mode of differentiation that is thought to induce loss of stem cell characteristics, promote neural lineage differentiation and a parallel loss of tumor initiation capacity. Here we show that GSCs retained both neurosphere formation and tumor initiation abilities after short or long term serum exposure. Under serum induced differentiating conditions, GSCs expressed both neural lineage and stem cell markers, highlighting the aberrant pseudo-differentiation state. GSCs maintained under adherent differentiating conditions continued to proliferate and initiate tumor formation with efficiencies similar to GSCs maintained under proliferating (neurosphere) conditions. Proneural (PN) GSCs under serum exposure showed an induction of mesenchymal (MES) gene expression signatures. Our data indicate that the tumor initiation ability of GSCs is independent of their differentiation state and that terminal differentiation as a therapeutic approach may not effectively negate tumorigenicity of GSCs. SIGNIFICANCE Terminal differentiation has been proposed as a therapeutic strategy for glioblastoma (GBM). Culturing of GBM derived tumor initiating glioma stem cells (GSCs) in fetal bovine serum containing media is a proposed mode of differentiation that is thought to induce loss of stem cell characteristics, promote neural lineage differentiation and a parallel loss of tumor initiation capacity. Here we show that GSCs retained both neurosphere formation and tumor initiation abilities after short or long term serum exposure. Under serum induced differentiating conditions, GSCs expressed both neural lineage and stem cell markers, highlighting the aberrant pseudo-differentiation state. GSCs maintained under adherent differentiating conditions continued to proliferate and initiate tumor formation with efficiencies similar to GSCs maintained under proliferating (neurosphere) conditions. Proneural (PN) GSCs under serum exposure showed an induction of mesenchymal (MES) gene expression signatures. Our data indicate that the tumor initiation ability of GSCs is independent of their differentiation state and that terminal differentiation as a therapeutic approach may not effectively negate tumorigenicity of GSCs.
2015-09-01 | GSE58923 | GEO
Project description:TET enzymes convert 5-methylcytosine to 5-hydroxymethylcytosine and higher oxidized derivatives. TETs stably associate with and are post-translationally modified by the nutrient-sensing enzyme OGT, suggesting a connection between metabolism and the epigenome. Here, we show for the first time that modification by OGT enhances TET1 activity in vitro. We identify a a domain of TET1 domain that is responsible necessary and sufficient for binding to OGT and report a point mutation that disrupts the TET1-OGT interaction. We show that the TET1-OGTthis interaction is necessary for TET1 to rescue hematopoetic stem cell production in tet mutant zebrafish embryos, suggesting that OGT promotes TET1’s function during development. Finally, we show that disrupting the TET1-OGT interaction in mouse embryonic stem cells changes the abundance of TET-containing high molecular weight complexesTET2 and 5-methylcytosine, which is accompanied by alterations in gene expression and causes widespread gene expression changes. These results link metabolism and epigenetic control, which may be relevant to the developmental and disease processes regulated by these two enzymes.
2018-11-02 | GSE119500 | GEO
Project description:Primary glioblastoma (GBM) cultures vary with respect to differentiation competency. We sought to identify putative transcription factors necessary for the differentiation of GBM cultures. In this dataset, we include expression data obtained from 2 human-fetal neural stem cell (HF-NS) cultures and 2 GBM stem cell (GSC) cultures. We assessed changes in gene expression from 3 timepoints during an in vitro differentiation protocol.
2017-07-13 | GSE87619 | GEO
Project description:Glioblastomas (GBM) are driven by malignant neural stem-like cells that display extensive heterogeneity and phenotypic plasticity, which drives tumour progression and therapeutic resistance. Here we show that the nodal extracellular matrix-cell adhesion protein integrin-linked kinase (ILK) is a key determinant of phenotypic plasticity and the mesenchymal-like, invasive cell state in mouse GBM stem cells. We found that an ILK-STAT3 signalling pathway is required for plasticity that enables the transition of GBM stem cells to an astrocyte-like state both in vitro andin vivo. GBM cells genetically depleted of ILK become predominantly stabilised in a transcriptionally-defined progenitor-like state that is characterised by lack of response to differentiation cues and constitutive proliferation. Loss of ILK or interference with STAT3 impairs differentiation potential, reducing phenotypic plasticity of tumour cell populations; additionally, ILK loss causes a mesenchymal- to epithelial-like morphological transition and suppression of malignancy-associated features. Our work defines ILK as a central regulator of multiple GBM phenotypes including phenotypic plasticity and mesenchymal state.
2023-08-07 | GSE240193 | GEO
Project description:Objective: Skeletal stem cells are known to be regulated by their local self-regulating niche, that is comprised mainly of their progeny and secreted paracrine factors. What cell intrinsic factors govern the maintenance and function of the SSC remains elusive. Methods: Using the previously characterized Tet1-/- mice we investigated the differences in skeletal stem cell lineage tree. Further we examined the ability of these cells to differentiate into osteogenic and chondrogenic lineages, both with and without injury. Transcriptomic differences and inflammatory cytokines were investigated for differences in cartilage development pathways. Results: Loss of Tet1 skews the SSC lineage tree by expanding the SSC pool at the expense of its progeny as well as by enhancing the chondrogenic differentiation of SSC and the multilineage bone cartilage stromal progenitors (BCSP). Tet1 inhibition leads to enhanced chondrogenesis in mouse BCSP upon injury, in human SSC and chondroprogenitors (CP) isolated from osteoarthritic (OA) human cartilage and in late stages of OA in a mouse model. Transcriptomic analyses of SSC and BCSP lacking Tet1 revealed dysregulated pathways including alterations in Tgfb signaling, melatonin degradation and cartilage development associated genes. Conclusion: Tet1 was identified as critical regulator of SSC fate. Loss of Tet1 selectively enhances chondrogenic ability of skeletal stem cells. Supplementation of melatonin can dampen inflammation and lead to better cartilage health.
2023-08-15 | GSE232666 | GEO
Project description:HIF-1α plays a crucial role in sustaining glioblastoma (GBM) cell growth and the maintenance of their undifferentiated phenotype. However, HIF-1α has been suggested to interplay with Wnt signaling components, thus activating a neuronal differentiation process in both GBM and normal brain. Here, we show that a β-catenin/TCF1/HIF-1α complex directly controls the transcription of neuronal differentiation genes in hypoxia. Conversely, at higher oxygen levels, the increased expression of TCF4 exerts a transcriptional inhibitory function on the same genomic regions, thus counteracting differentiation. Moreover, we demonstrate the existence of a positive correlation between HIF-1α, TCF1 and neuronal phenotype in GBM tumors, accompanied by the over-expression of several Wnt signaling components, finally impacting on patient prognosis. In conclusion, we unveil a mechanism by which TCF1 and HIF-1α induce a reminiscent neuronal differentiation of hypoxic GBM cells, which is hampered, in normoxia, by high levels of TCF4, thus de facto sustaining cell aggressiveness. In this study we unveil a tightly regulated mechanism by which HIF-1α controls the balance of Wnt signaling co-factors and how their molecular interplay regulates the peculiar transcriptional events responsible for the phenotypic shift of GBM stem cells toward a reminiscent neuronal differentiation, which might represent a future potential strategy to therapeutically weaken their aggressiveness.
2019-08-21 | GSE113512 | GEO
Project description:We cultured tumor cells from 22 GBM under medium conditions favoring the growth of neural stem cells. 11 out of 15 primary GBM contained a significant CD133+ subpopulation that comprised cells showing all hallmarks of neural stem cells. Cell lines derived from these CD133+ GBM showed a neurosphere-like, non-adherent growth pattern. In contrast, 4 out of 15 cell lines derived from primary GBM grew adherent in vitro and were driven by CD133- tumor cells that fulfilled stem cell criteria. In vivo, these GBM were characterized by a significantly lower proliferation index but similar GFAP staining as compared to CD133+ GBM. Gene arrays from 2x3 representative cells lines are given. Experiment Overall Design: Human glioblastoma cells cultured in DMEM supplemented with EGF, FGF, LIF, B27.
2007-11-01 | E-GEOD-7181 | biostudies-arrayexpress