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 heterogenity in childhood EPN. PFA subgroup EPNs concealed an undifferentiated progenitor subpopulation that either differentiated into subpopulations with ependymal cell characteristics, or transitioned into a mesenchymal subpopulation. Undifferentiated and mesenchymal PFA subpopulations were associated with a poor prognosis, providing new therapeutic targets. In conflict with current classification paradigms, relative PFA subpopulation proportions were shown to determine bulk-tumor assigned subgroups. This atlas of EPN cellular heterogeneity provides an important advance in our understanding of EPN biology.
Published Version
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