GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE125969 Query DataSets for GSE125969
Status Public on Jul 31, 2020
Title Ependymoma subpopulation lineages underlie clinical classification and outcome (scRNAseq data set)
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Ependymoma (EPN) is a brain tumor commonly presenting in childhood that remains fatal in the majority of children. Intra-tumoral cellular heterogeneity in bulk tumor samples significantly confounds our understanding of EPN biology, impeding development of effective therapy. We used single-cell RNA sequencing to identify four neoplastic cell subpopulations in posterior fossa EPN patient samples that underlie traditional subgroup classification and harbor divergent lineage trajectories and clinical outcomes. Neoplastic subpopulations expressed gene signatures associated with normal ependyma, ependymoma, and mesenchymal phenotypes, consequently named ciliated (CEC), transportive (TEC), undifferentiated (UEC), and mesenchymal ependymoma cells (MEC). The abundance of EPN subpopulations as estimated by deconvolution of EPN bulk tumor transcriptomes showed that the ratio of MEC and CEC cell fractions dictated assignment to the two main classification subgroups in PFA. Longitudinal analysis revealed evolution of subpopulation fractions, notably MEC and CEC, which changed between presentation and recurrence. Outcome analyses demonstrated that a higher proportion of UEC or MEC subpopulations was associated with shorter survival, whereas CEC was associated with longer survival. Unsupervised pseudotime analysis revealed divergent subpopulation lineages. The first lineage conformed to a classic cancer stem cell trajectory where UEC progenitors differentiate sequentially to TECs and then CECs. In the second trajectory MECs arise from UECs via TECs, potentially in response to hypoxia-mediated cellular stress, a process that we recreated in vitro in a hypoxia treated EPN cell line. Our study reveals the existence of significant, unappreciated cellular heterogeneity in EPN and provides important resolution of EPN tumor biology.
Overall design Single-cell transcriptional profiles (10X Chromium) were generated from ten EPN-PF classified as PFA1 (n=6) and PFA2 (n=4) based on bulk tumor methylomic and transcriptomic profiling.
Contributor(s) Gillen AE, Riemondy KA, Gilani A, Venkataraman S, Madhavan K, Prince E, Sanford B, Amani V, Griesinger A, Hankinson T, Handler M, Vibhakar R, Jones K, Mitra S, Hesselberth JR, Foreman N, Donson A
Citation(s) 32783945
Submission date Jan 31, 2019
Last update date Apr 15, 2021
Contact name Andrew M Donson
Phone 303 724 4012
Organization name CU Anschutz Medical Campus
Department Pediatrics
Lab RC1 North, P18-4401M
Street address 12800 E 19th Ave
City Aurora
State/province CO
ZIP/Postal code 80010
Country USA
Platforms (2)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (26)
GSM4132013 EPN_1239
GSM4132014 EPN_723
GSM4132015 EPN_727
This SubSeries is part of SuperSeries:
GSE126025 Ependymoma subpopulation lineages underlie clinical classification and outcome
BioProject PRJNA518131
SRA SRP183083

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE125969_cell_metadata.tsv.gz 686.9 Kb (ftp)(http) TSV
GSE125969_count_matrix.tsv.gz 39.3 Mb (ftp)(http) TSV
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap