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An OTX2-PAX3 signaling axis regulates Group 3 medulloblastoma cell fate [scRNA-seq]

ABSTRACT: An OTX2-PAX3 signaling axis regulates Group 3 medulloblastoma cell fate [scRNA-seq]

PROVIDER: PRJNA566451 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10149824_1.fastq.gz	Fastqsanger.gz
	SRR10149824_2.fastq.gz	Fastqsanger.gz
	SRR10149825_1.fastq.gz	Fastqsanger.gz
	SRR10149825_2.fastq.gz	Fastqsanger.gz
	SRR10149826_1.fastq.gz	Fastqsanger.gz

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An OTX2-PAX3 signaling axis regulates Group 3 medulloblastoma cell fate

Project description:An OTX2-PAX3 signaling axis regulates Group 3 medulloblastoma cell fate

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An OTX2-PAX3 signaling axis regulates Group 3 medulloblastoma cell fate [scRNA-seq]

Project description:scRNA-seq was performed to evaluate the OTX2-PAX3-mTOR signalling axis at the single cell level in heterogeneous Group 3 MB tumorspheres

2020-06-11 | GSE137758 | GEO

An OTX2-PAX3 signaling axis regulates Group 3 medulloblastoma cell fate [ChIP-seq]

Project description:An OTX2-PAX3 signaling axis regulates Group 3 medulloblastoma cell fate [ChIP-seq]

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An OTX2-PAX3 signaling axis regulates Group 3 medulloblastoma cell fate [RNA-seq]

Project description:An OTX2-PAX3 signaling axis regulates Group 3 medulloblastoma cell fate [RNA-seq]

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An OTX2-PAX3 signaling axis regulates Group 3 medulloblastoma cell fate [ChIP-seq]

Project description:We evaluated changes in active and repressive histone modifications following the silencing of OTX2 in Group 3 medulloblastoma tumorspheres

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An OTX2-PAX3 signaling axis regulates Group 3 medulloblastoma cell fate.

Project description:OTX2 is a potent oncogene that promotes tumor growth in Group 3 medulloblastoma. However, the mechanisms by which OTX2 represses neural differentiation are not well characterized. Here, we perform extensive multiomic analyses to identify an OTX2 regulatory network that controls Group 3 medulloblastoma cell fate. OTX2 silencing modulates the repressive chromatin landscape, decreases levels of PRC2 complex genes and increases the expression of neurodevelopmental transcription factors including PAX3 and PAX6. Expression of PAX3 and PAX6 is significantly lower in Group 3 medulloblastoma patients and is correlated with reduced survival, yet only PAX3 inhibits self-renewal in vitro and increases survival in vivo. Single cell RNA sequencing of Group 3 medulloblastoma tumorspheres demonstrates expression of an undifferentiated progenitor program observed in primary tumors and characterized by translation/elongation factor genes. Identification of mTORC1 signaling as a downstream effector of OTX2-PAX3 reveals roles for protein synthesis pathways in regulating Group 3 medulloblastoma pathogenesis.

| S-EPMC7371715 | biostudies-literature

An OTX2-PAX3 signaling axis regulates Group 3 medulloblastoma cell fate [RNA-seq]

Project description:RNA-seq was carried out to evaluate the molecular mechanisms that contribute to the distinguishing effects of PAX3 and PAX6 GOF on Group 3 MB cells

2020-06-11 | GSE132506 | GEO

OTX2 drives medulloblastoma proliferation via direct regulation of cell cycle genes and inhibits differentiation

Project description:The transcription factor OTX2 has been implicated as an oncogene in medulloblastoma, which is the most common malignant brain tumor in children. It is highly expressed in most medulloblastomas and amplified in a subset of them. The role of OTX2 in medulloblastoma and its downstream targets are unclear. Therefore, we generated D425 medulloblastoma cells in which we can silence endogenous OTX2 by inducible shRNA. Silencing of OTX2 strongly inhibited cell proliferation and resulted in a neuronal-like differentiation. Expression profiling of time courses after silencing showed a progressive change in gene expression for many cellular processes. Down regulated genes were highly enriched for cell cycle and visual perception genes, while up regulated genes were enriched for genes involved in development and differentiation. This shift in expression profiles is reminiscent to changes described to occur during normal cerebellum development. OTX2 is expressed in proliferating granular progenitor cells, but the expression diminishes when these cells exit the cell cycle and start differentiating. ChIP-on-chip analyses of OTX2 in D425 cells showed that cell cycle and perception genes were direct OTX2 targets, while regulation of most differentiation genes appears to be indirect. These analyses provide the first insight in the molecular network of OTX2, demonstrating that OTX2 is essential in medulloblastoma and directly drives proliferation by regulating the expression of cell cycle genes. Since many of these genes also correlate in expression with OTX2 in primary tumors, they might be potential targets for therapy in medulloblastoma patients. Keywords: OTX2, medulloblastoma, mRNA profiling *** This Series represents the gene expression component of the study. Three independent time course experiments of OTX2 silencing, and 1 control experiment in D425 medulloblastoma cells.

2012-07-03 | E-GEOD-22875 | biostudies-arrayexpress

OTX2 drives medulloblastoma proliferation via direct regulation of cell cycle genes and inhibits differentiation

2012-07-04 | GSE22875 | GEO

An OTX2-PAX3 signaling axis regulates Group 3 medulloblastoma cell fate

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-06-11 | GSE132558 | GEO