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Single-Cell RNA Sequencing of Childhood Ependymoma Reveals Neoplastic Cell Subpopulations That Impact Molecular Classification and Etiology.

Cell reports | 2020

Ependymoma (EPN) is a brain tumor commonly presenting in childhood that remains fatal in most children. Intra-tumoral cellular heterogeneity in bulk-tumor samples significantly confounds our understanding of EPN biology, impeding development of effective therapy. We, therefore, use single-cell RNA sequencing, histology, and deconvolution to catalog cellular heterogeneity of the major childhood EPN subgroups. Analysis of PFA subgroup EPN reveals evidence of an undifferentiated progenitor subpopulation that either differentiates into subpopulations with ependymal cell characteristics or transitions into a mesenchymal subpopulation. Histological analysis reveals that progenitor and mesenchymal subpopulations co-localize in peri-necrotic zones. In conflict with current classification paradigms, relative PFA subpopulation proportions are shown to determine bulk-tumor-assigned subgroups. We provide an interactive online resource that facilitates exploration of the EPN single-cell dataset. This atlas of EPN cellular heterogeneity increases understanding of EPN biology.

Pubmed ID: 32783945 RIS Download

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: P30 CA046934
  • Agency: NCI NIH HHS, United States
    Id: R01 CA237608
  • Agency: NIGMS NIH HHS, United States
    Id: R35 GM119550
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM136444

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This is a list of tools and resources that we have found mentioned in this publication.


Ivy Glioblastoma Atlas Project (tool)

RRID:SCR_005044

Platform for exploring the anatomic and genetic basis of glioblastoma at the cellular and molecular levels that includes two interactive databases linked together by de-identified tumor specimen numbers to facilitate comparisons across data modalities: * The open public image database, here, providing in situ hybridization data mapping gene expression across the anatomic structures inherent in glioblastoma, as well as associated histological data suitable for neuropathological examination * A companion database (Ivy GAP Clinical and Genomic Database) offering detailed clinical, genomic, and expression array data sets that are designed to elucidate the pathways involved in glioblastoma development and progression. This database requires registration for access. The hope is that researchers all over the world will mine these data and identify trends, correlations, and interesting leads for further studies with significant translational and clinical outcomes. The Ivy Glioblastoma Atlas Project is a collaborative partnership between the Ben and Catherine Ivy Foundation, the Allen Institute for Brain Science and the Ben and Catherine Ivy Center for Advanced Brain Tumor Treatment.

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Bioconductor (tool)

RRID:SCR_006442

Software repository for R packages related to analysis and comprehension of high throughput genomic data. Uses separate set of commands for installation of packages. Software project based on R programming language that provides tools for analysis and comprehension of high throughput genomic data.

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Cufflinks (tool)

RRID:SCR_014597

Software tool for transcriptome assembly and differential expression analysis for RNA-Seq. Includes script called cuffmerge that can be used to merge together several Cufflinks assemblies. It also handles running Cuffcompare as well as automatically filtering a number of transfrags that are likely to be artifacts. If the researcher has a reference GTF file, the researcher can provide it to the script to more effectively merge novel isoforms and maximize overall assembly quality.

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Caveolin 1 Polyclonal Antibody (antibody)

RRID:AB_2549770

This unknown targets Caveolin 1

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VPAC2 Polyclonal Antibody (antibody)

RRID:AB_2216680

This unknown targets VPAC2

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GLUT1 antibody (antibody)

RRID:AB_10837075

This polyclonal targets GLUT1

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Anti-FOXJ1 antibody produced in rabbit (antibody)

RRID:AB_1078902

This unknown targets Forkhead box protein J1 recombinant protein epitope signature tag

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COL9A2 Polyclonal Antibody (antibody)

RRID:AB_2640030

This unknown targets COL9A2

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Calcyphosine Antibody (antibody)

RRID:AB_11016241

This unknown targets Calcyphosine

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Carbonic Anhydrase IX Antibody (antibody)

RRID:AB_10003398

This unknown targets Carbonic Anhydrase IX

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