Single-cell RNA-seq of pediatric ependymoma
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ABSTRACT:
PROVIDER: PRJNA593551 | ENA |
REPOSITORIES: ENA
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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: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: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:Single-Cell RNA Sequencing of Pediatric Ependymoma uncovers Subclonal Heterogeneity associated with Patient Survival
| PRJNA785181 | ENA
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: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.
2013-08-30 | E-GEOD-50385 | biostudies-arrayexpress
Project description:Ependymoma is a malignant glial tumor occurring throughout central nervous system, with one third of relapse rate. The increasing accessibility of single-cell transcriptome has accelerated our understanding of ependymoma. In this study, we generated a high-resolution single-cell dataset with a particular focus on the comparison of subclonal differences within tumor populations. As a proxy to traditional pseudotime analysis, we developed a novel trajectory scoring method to predict survival outcomes and specific molecular characteristics. Moreover, we identified putative cell-cell communication features between relapsed and primary samples and show upregulation of pathways associated with immune cell crosstalk. Our results reveal both inter- and intratumoral gene expression profiles and tumor differentiation and provide a framework for future studies on transcriptomic signatures of individual subclones in brain tumors at single-cell resolution, by which could complement existing published datasets and provide valuable insights into cell-type-specific properties and lay the foundation for therapeutic treatments of diseases.
2022-06-15 | GSE189939 | GEO
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