Single-cell RNA-seq of pediatric ependymoma
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ABSTRACT:
PROVIDER: PRJNA593551 | ENA |
REPOSITORIES: ENA
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Project description:Single cell multiome atlas of pediatric ependymoma
| PRJNA1124137 | ENA
Project description:Despite extensively growing knowledge on the molecular biology of ependymoma, effective treatments are still lacking for about half patients with high-risk tumors. By applying single cell RNA-sequencing, we comprehensively identify a cellular hierarchy within ependymoma spanning undifferentiated and differentiated tumor cell states across all major molecular groups. This not only refines the concept of these established molecular groups but moreover provides a biological context for the well-known capacity of aggressive ependymomas for late recurrence and treatment resistance. Our newly defined transcriptomic signatures also prove to be of prognostic relevance within established high-risk ependymoma groups. Consequently, the newly characterized cell states could serve as promising future therapeutic targets and biomarkers for clinical trials.
2020-07-13 | GSE141460 | GEO
Project description:ZFTA-RELA is the most recurrent genetic alteration seen in ependymoma, and sufficient to initiate tumors when expressed during mouse brain development. Despite ZFTA-RELA’s potent oncogenic potential, ZFTA-RELA gene fusions are observed exclusively in ependymoma and have never been documented in any other adult or pediatric malignancy. We hypothesized that specific chromatin modules accessible during brain development would render specific cells-of-origin at increased risk of transformation by ZFTA fusion proteins. To this end we performed integrated single cell ATAC and RNA-seq analysis (referred to as scMultimome) in mouse and human ependymoma tumors driven by the ZFTA-RELA fusion. We demonstrate that specific epi-developmental programs present in radial glia and regulated by Plagl1 are at direct risk of transformation. Oncoprotein engagement of this chromatin module leads to persistent oncogene expression, a failure to halt cellular proliferation, and initiate terminal cellular differentiation. Surprisingly, ependymomas exhibit significant heterogeneity across lineage differentiation programs, and continued activation of Plagl1 networks in differentiated cell types such as tumor neuronal-like cells contribute to tumor progression. These findings implicate specific chromatin modules in cells of origin as critical mediators of ependymoma initiation. Persistent activation and erosion of developmetn lineage programs serve as drivers of tumor development and contribute to the cellular heterogeneity of the tumor microenvironment.
2026-03-25 | GSE269937 | GEO
Project description:Pediatric ependymoma has relatively low frequencies of DNA mutations, which suggest that epigenetics may drive tumors. However, the epigenetic mechanisms for recurrent ependymoma are still poorly understood. Here, we performed longitudinal and comprehensive DNA methylation and gene expression analysis for recurrent pediatric ependymoma tumors from 10 patients, total 46 DNA methylomes (including primary tumors and matched recurrent tumors; normal pediatric brain tissues and PDOX tumors). Both RELA and PFA tumors maintained the subtype DNA methylation signatures during repeated relapses. We further identified the potential DNA methylation predictors, drivers and boosters and their potential regulated genes for recurrent ependymoma tumors. Increased DNA methylation levels within H3K4me1 enriched regions indicates disturbed functions of LSD1 gene in recurrent ependymoma tumors. Combining novel LSD1 inhibitor SYC-836 with radiation (XRT) significantly prolonged animal survival times in PDOX models of recurrent PFA ependymoma. Our PDOX models provide a unique platform for preclinical testing drugs and development of new therapy for pediatric recurrent ependymoma.
2022-07-12 | GSE156619 | GEO
Project description:Single-Cell RNA Sequencing of Pediatric Ependymoma uncovers Subclonal Heterogeneity associated with Patient Survival
| PRJNA785181 | ENA
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
Project description:We compared genomic characteristics of primary and first recurrent pediatric ependymoma to identify sub-group specific differences.
2016-09-11 | GSE50876 | GEO
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 | GSE206579 | GEO
Project description:Epigenetic Landscape of Pediatric Ependymoma Recurrence
| PRJNA658524 | ENA
Project description:Ependymoma is a heterogeneous entity of central nervous system tumors with well-established molecular groups. Here, we apply single-cell RNA sequencing to analyze ependymomas across molecular groups and anatomic locations to investigate their intratumoral heterogeneity and developmental origins. Ependymomas are composed of a cellular hierarchy initiating from undifferentiated populations, which undergo impaired differentiation toward three lineages of neuronal-glial fate specification. While prognostically favorable groups of ependymoma predominantly harbor differentiated cells, aggressive groups are enriched for undifferentiated cell populations. The delineated transcriptomic signatures correlate with patient survival and define molecular dependencies for targeted treatment approaches. Taken together, our analyses reveal a developmental hierarchy underlying ependymomas relevant to biological and clinical behavior.
| S-EPMC7479515 | biostudies-literature