bioRxivDevelopmental BiologyPreprint
Ependymomas are cancers of the pre-neural crest/roof plate lineage
Polina BaliniD, Sachin A Kumar, Riley GaltoniD, Alberto DelaidelliiD, Wilda OrismeiD, Parthiv HaldipuriD, Ncedile Mankahla, Amr M. SaadeldiniD, Nik von Krosigk, Maria Claudia VladoiuiD, Anders Wilder EricksoniD, Meyer Barembaum, Jake MillmaniD, Amy J Banks, Jeffrey T Joseph, Omar Khan, Simon Du, Olga SirbuiD, Winnie Ong, Damien FauryiD, Vicente Santa Maria Lopez, Sigourney Bonner, Jennifer C. ColemaniD, Jason EigenbroodiD, Elizabeth Alexandra CooperiD, , Michael D. TayloriD
Abstract
Distinct molecular variants of the brain cancer ependymoma are distributed along the rostral-caudal extent of the central nervous system (CNS). Historically proposed to arise from ventricular ependyma, recent studies have suggested conflicting cellular origins, including the neural radial glia and the roof plate lineages. Using single-cell transcriptomics, immunohistochemistry, and lineage tracing, we demonstrate that ependymomas across all CNS compartments transcriptionally mirror MSX1+ve pre-neural crest/roof plate (Pre-NC/RP) lineage derivatives. Ependymoma subgroups recapitulate the spatial and molecular diversity of regional Pre-NC/RP populations, while retaining conserved MSX1 expression. Expression of the oncogenic fusion ZFTA-RELA within the murine Pre-NC/RP lineage generated tumors that faithfully resembled human ependymoma. These findings identify a common embryonic cellular origin for ependymomas and reconcile previously conflicting models of tumorigenesis.
- organism: mouse
- organism: human
- assay: scRNA-seq
- assay: imaging
- research focus: cell type annotation
- research focus: clustering
- research focus: differential expression
- research focus: gene regulatory network inference
- approach: statistical model
- approach: experimental assay
- Citations
- 0
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