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Pro-Inflammatory Cytokines Mediate the Epithelial-to-Mesenchymal-Like Transition of Pediatric Posterior Fossa Ependymoma (single-nucleus ATAC-seq)

ABSTRACT: Pediatric ependymoma is a devastating brain cancer marked by its relapsing pattern and lack of effective chemotherapies. This shortage of treatments is due to limited knowledge about ependymoma tumorigenic mechanisms. By means of single-nucleus chromatin accessibility and gene expression profiling of posterior fossa primary tumors and distal metastases, we reveal key transcription factors and enhancers associated with the differentiation of ependymoma tumor cells into tumor-derived cell lineages and their transition into a mesenchymal-like state. We identify NFkB, AP-1, and MYC as mediators of this transition, and show that the gene expression profiles of tumor cells and infiltrating microglia are consistent with abundant pro-inflammatory signaling between these populations. In line with these results, both TGF-b1 and TNF-a induce the expression of mesenchymal genes on a patient-derived cell model, and TGF-b1 leads to an invasive phenotype. Altogether, these data suggest that tumor gliosis induced by inflammatory cytokines and oxidative stress underlies the mesenchymal phenotype of posterior fossa ependymoma.

ORGANISM(S): Homo sapiens

PROVIDER: GSE206579 | GEO | 2022/06/24

REPOSITORIES: GEO

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Pro-Inflammatory Cytokines Mediate the Epithelial-to-Mesenchymal-Like Transition of Pediatric Posterior Fossa Ependymoma (single-nucleus RNA-seq)

Project description:Pediatric ependymoma is a devastating brain cancer marked by its relapsing pattern and lack of effective chemotherapies. This shortage of treatments is due to limited knowledge about ependymoma tumorigenic mechanisms. By means of single-nucleus chromatin accessibility and gene expression profiling of posterior fossa primary tumors and distal metastases, we reveal key transcription factors and enhancers associated with the differentiation of ependymoma tumor cells into tumor-derived cell lineages and their transition into a mesenchymal-like state. We identify NFkB, AP-1, and MYC as mediators of this transition, and show that the gene expression profiles of tumor cells and infiltrating microglia are consistent with abundant pro-inflammatory signaling between these populations. In line with these results, both TGF-b1 and TNF-a induce the expression of mesenchymal genes on a patient-derived cell model, and TGF-b1 leads to an invasive phenotype. Altogether, these data suggest that tumor gliosis induced by inflammatory cytokines and oxidative stress underlies the mesenchymal phenotype of posterior fossa ependymoma.

2022-06-24 | GSE206578 | GEO

Pro-Inflammatory Cytokines Mediate the Epithelial-to-Mesenchymal-Like Transition of Pediatric Posterior Fossa Ependymoma

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Project description:Two distinct groups of posterior fossa ependymoma, PF-EPN-A and PF-EPN-B have been identified in children and are often associated with widely distinct outcomes. We have identified an ultra-high-risk PF-EPN-A ependymoma with 6q loss. We performed RNA sequencing of posterior fossa ependymoma A (PF-EPN-A) tumor samples with chromosome 6q loss and balanced to understand the differences in 6q loss at the transcriptomic level

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Whole-genome microRNA microarray for CD44 positive and negative pediatric posterior fossa ependymoma

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Expression data from human ependymoma

Project description:We compared molecular characteristics of primary and recurrent pediatric ependymoma to identify sub-group specific differences. Gene expression profiles were used to identify unique immunobiologic sub-types of posterior fossa pediatric ependymoma. Gene expression profiles were generated from surgical tumor (ependymoma) (n=65) using Affymetrix HG-U133plus2 chips (Platform GPL570). Normalization was performed on our entire cohort of ependymoma. Of the 65 samples, a sub-set of 58 were used in the corresponding manuscript. Excluded samples are noted. Gene expression profiles were filtered to obtain gene expression of key immune cell markers. Comparative analyses between tumor samples were used to identifiy unique immunobiology between posterior fossa sub-groups.

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Delineation of Two Clinically and Molecularly Distinct Subgroups of Posterior Fossa Ependymoma.

Project description:Despite histological similarity of ependymomas from throughout the neuraxis, the disease likely comprises multiple independent entities, each with a distinct molecular pathogenesis. Transcriptional profiling of two large independent cohorts of ependymomas reveals the existence of two demographically, transcriptionally, genetically and clinically distinct groups of posterior fossa (PF) ependymoma. Group A patients are younger, have laterally located tumors with a balanced genome, and are much more likely to exhibit recurrence, metastasis, and death as compared to Group B patients. Identification and optimization of immunohistochemical markers for PF ependymoma subgroups allowed validation of our findings on a third group of independent ependymomas using a human ependymoma tissue microarray, and provides a tool for prospective prognostication and stratification of PF ependymoma patients. This SuperSeries is composed of the following subset Series: GSE27283: Human ependymoma samples [expression] GSE27286: Human ependymoma samples, Subgrouping [aCGH - German Cancer Research Center human 33K BAC array] Refer to individual Series

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Project description:Gene expression (mRNA) profiling of human ependymomas Despite the histological similarity of ependymomas from throughout the neuraxis, the disease likely comprises multiple independent entities, each with a distinct molecular pathogenesis. Transcriptional profiling of two large independent cohorts of ependymoma reveals the existence of two demographically, transcriptionally, genetically, and clinically distinct groups of posterior fossa (PF) ependymoma. Group-A patients are younger, have laterally located tumors with a balanced genome, and are much more likely to exhibit recurrence, secondary metastasis, and death as compared to Group-B patients. Identification and optimization of immunohistochemical markers for PF ependymoma subgroups allowed validation of our findings on a third independent group of tumors using a human ependymoma tissue microarray, and provides a tool for prospective prognostication and stratification of PF ependymoma patients. We analyzed 102 primary ependymomas on the Affymetrix Exon 1.0ST platform (Gene Level).

2011-08-14 | E-GEOD-27279 | biostudies-arrayexpress

High and low cell density areas in posterior fossa ependymoma type A have a distinct transcriptome

Project description:Posterior fossa type A (PF-EPN-A, PFA) ependymoma are aggressive tumors that mainly affect children and have a poor prognosis. Histopathology shows significant intratumoral heterogeneity, ranging from loose tissue to often sharply demarcated, extremely cell dense tumor areas. Spatial transcriptomics of six cases allow for a comparison of the transcriptome of high and low cell density areas.

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