EPEN-31. SINGLE-CELL RNAseq OF CHILDHOOD EPENDYMOMA REVEALS DISTINCT NEOPLASTIC CELL SUBPOPULATIONS THAT IMPACT ETIOLOGY, MOLECULAR CLASSIFICATION AND OUTCOME. (4th December 2020)

• Record Type: Journal Article
• Authors: Donson, Andrew; Gillen, Austin; Kent, Riemondy; Gilani, Ahmed; Venkataraman, Sujatha; Sanford, Bridget; Griesinger, Andrea; Amani, Vladimir; Hankinson, Todd; Handler, Michael; Hesselberth, Jay; Vibhakar, Rajeev; Foreman, Nicholas
• Is Part Of: Neuro-oncology. Volume 22(2020)Supplement 3
• Page Start: iii314
• Page End: iii314
• Publication Date: 2020-12-04
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noaa222.167
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: 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 therefore used single-cell RNA sequencing to catalog cellular heterogeneity of 26 childhood EPN, predominantly from ST-RELA, PFA1 and PFA2 subgroups. ST-RELA and PFA subgroups clustered separately, with ST-RELA clustering largely according to individual sample-of-origin. PFA1 and PFA2 subgroup EPNs cells were intermixed and revealed 4 major subpopulations – 2 with characteristics of ependymal differentiation (transporter and ciliated phenotype subpopulations), an undifferentiated subpopulation and a mesenchymal phenotype. Pseudotime analysis showed the undifferentiated progenitor subpopulation either differentiating into ependymal differentiation subpopulations or transitioning into the mesenchymal subpopulation. Histological analysis revealed that undifferentiated and mesenchymal subpopulations cells colocalized to perinecrotic/perivascular zones, the putative ependymoma stem cell niche. Deconvolution of PFA bulk transcriptome data showed that undifferentiated and mesenchymal subpopulations were associated with a poor prognosis; whereas the ciliated ependymal cell-differentiated subpopulation was associated with a good prognosis. In conflict with current distinct classification paradigms, the ratio of mesenchymal and ciliated subpopulations determined bulk-tumor subgroups assignment to PFA1 and PFA2 respectively. This atlas of EPN cellular heterogeneity provides an important advance in our understanding of EPN biology, identifying high-risk associated subpopulations for therapeutic targeting.