Details

Autor(en) / Beteiligte

• Gojo, Johannes
• Englinger, Bernhard
• Jiang, Li
• Hübner, Jens M.
• Shaw, McKenzie L.
• Hack, Olivia A.
• Madlener, Sibylle
• Kirchhofer, Dominik
• Liu, Ilon
• Pyrdol, Jason
• Hovestadt, Volker
• Mazzola, Emanuele
• Mathewson, Nathan D.
• Trissal, Maria
• Lötsch, Daniela
• Dorfer, Christian
• Haberler, Christine
• Halfmann, Angela
• Mayr, Lisa
• Peyrl, Andreas
• Geyeregger, Rene
• Schwalm, Benjamin
• Mauermann, Monica
• Pajtler, Kristian W.
• Milde, Till
• Shore, Marni E.
• Geduldig, Jack E.
• Pelton, Kristine
• Czech, Thomas
• Ashenberg, Orr
• Wucherpfennig, Kai W.
• Rozenblatt-Rosen, Orit
• Alexandrescu, Sanda
• Ligon, Keith L.
• Pfister, Stefan M.
• Regev, Aviv
• Slavc, Irene
• Berger, Walter
• Suvà, Mario L.
• Kool, Marcel
• Filbin, Mariella G.

Titel

Single-Cell RNA-Seq Reveals Cellular Hierarchies and Impaired Developmental Trajectories in Pediatric Ependymoma

Ist Teil von

• Cancer cell, 2020-07, Vol.38 (1), p.44-59.e9

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• 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. [Display omitted] •Cellular hierarchies in ependymoma reflect impaired neurodevelopment•Ependymoma cells follow neuronal-, astrocytic-, and ependymal-like trajectories•Undifferentiated programs confer inferior prognosis and are enriched at recurrence•Preclinical data suggest feasibility of inhibiting undifferentiated subpopulations Gojo et al. use single-cell RNA sequencing to investigate intratumoral heterogeneity and cellular hierarchy in pediatric ependymoma, identifying impaired neurodevelopmental trajectories. The malignant trajectories reveal therapeutic targets and prognostic signatures in ependymoma.