Single-cell RNA-seq reveals cellular hierarchies and impaired developmental trajectories in pediatric ependymoma
Ependymoma is a heterogeneous entity of central nervous system tumors with well-established molecular groups. Here, we apply single-cell RNA sequencing to analyze ependymomas across molecular groups and anatomic locations to investigate their intratumoral heterogeneity and developmental origins. Epe...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
July 13, 2020
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| In: |
Cancer cell
Year: 2020, Volume: 38, Issue: 1, Pages: 44-59.e9 |
| ISSN: | 1878-3686 |
| DOI: | 10.1016/j.ccell.2020.06.004 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.ccell.2020.06.004 Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S1535610820303081 
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| Author Notes: | Johannes Gojo, Bernhard Englinger, Li Jiang, Jens M. Hübner, McKenzie L. Shaw, Olivia A. Hack, Sibylle Madlener, Dominik Kirchhofer, Ilon Liu, Jason Pyrdol, Volker Hovestadt, Emanuele Mazzola, Nathan D. Mathewson, Maria Trissal, Daniela Lötsch, Christian Dorfer, Christine Haberler, Angela Halfmann, Lisa Mayr, Andreas Peyrl, Rene Geyeregger, Benjamin Schwalm, Monica Mauermann, Kristian W. Pajtler, Till Milde, Marni E. Shore, Jack E. Geduldig, Kristine Pelton, Thomas Czech, Orr Ashenberg, Kai W. Wucherpfennig, Orit Rozenblatt-Rosen, Sanda Alexandrescu, Keith L. Ligon, Stefan M. Pfister, Aviv Regev, Irene Slavc, Walter Berger, Mario L. Suvà, Marcel Kool, and Mariella G. Filbin |
| Summary: | Ependymoma is a heterogeneous entity of central nervous system tumors with well-established molecular groups. Here, we apply single-cell RNA sequencing to analyze ependymomas across molecular groups and anatomic locations to investigate their intratumoral heterogeneity and developmental origins. Ependymomas are composed of a cellular hierarchy initiating from undifferentiated populations, which undergo impaired differentiation toward three lineages of neuronal-glial fate specification. While prognostically favorable groups of ependymoma predominantly harbor differentiated cells, aggressive groups are enriched for undifferentiated cell populations. The delineated transcriptomic signatures correlate with patient survival and define molecular dependencies for targeted treatment approaches. Taken together, our analyses reveal a developmental hierarchy underlying ependymomas relevant to biological and clinical behavior. |
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| Item Description: | Gesehen am 08.09.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1878-3686 |
| DOI: | 10.1016/j.ccell.2020.06.004 |