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bioRxiv · 10.1101/2022.02.26.482082

Single-cell RNA Sequencing of Pediatric Ependymoma Unravels Subclonal Heterogeneity Associated with Patient Survival

Wu, H.·Jin, W.·Zhang, Y.-H.·Liu, Z.·Chen, Z.·Xu, J.·Tian, Y.·Wong, S. Z. H.·Wu, Q.-F.
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Abstract

Ependymoma (EPN) is a malignant glial tumor occurring throughout central nervous system which commonly presents in children. Although recent studies have characterized EPN samples at both the bulk and single-cell level, intra-tumoral heterogeneity across subclones remains a confounding factor which impedes understanding of EPN biology. In this study, we generated a high-resolution single-cell dataset of pediatric ependymoma with a particular focus on the comparison of subclone differences within tumors, and show upregulation of cilium-associated genes in more highly differentiated subclone populations. As a proxy to traditional pseudotime analysis, we applied a novel trajectory scoring method to reveal cellular compositions associated with poor survival outcomes across primary and relapsed patients. Furthermore, 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 studying transcriptomic signatures of individual subclones in ependymoma at single-cell resolution.

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Wu, H., Jin, W., Zhang, Y.-H., Liu, Z., Chen, Z., Xu, J., Tian, Y., Wong, S. Z. H., Wu, Q.-F.. 2022-03-01. Single-cell RNA Sequencing of Pediatric Ependymoma Unravels Subclonal Heterogeneity Associated with Patient Survival. https://doi.org/10.1101/2022.02.26.482082

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