Single-Cell RNA Sequencing of Childhood Ependymoma Reveals Neoplastic Cell Subpopulations That Impact Molecular Classification and Etiology
Austin E. Gillen,
Kent A. Riemondy,
Vladimir Amani,
Andrea M. Griesinger,
Ahmed Gilani,
Sujatha Venkataraman,
Krishna Madhavan,
Eric Prince,
Bridget Sanford,
Todd C. Hankinson,
Michael H. Handler,
Rajeev Vibhakar,
Ken L. Jones,
Siddhartha Mitra,
Jay R. Hesselberth,
Nicholas K. Foreman,
Andrew M. Donson
Affiliations
Austin E. Gillen
RNA Biosciences Initiative, University of Colorado Denver, Aurora, CO 80045, USA
Kent A. Riemondy
RNA Biosciences Initiative, University of Colorado Denver, Aurora, CO 80045, USA
Vladimir Amani
Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children’s Hospital Colorado, Aurora, CO 80045, USA; Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045, USA
Andrea M. Griesinger
Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children’s Hospital Colorado, Aurora, CO 80045, USA; Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045, USA
Ahmed Gilani
Department of Pathology, University of Colorado Denver, Aurora, CO 80045, USA
Sujatha Venkataraman
Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children’s Hospital Colorado, Aurora, CO 80045, USA; Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045, USA
Krishna Madhavan
Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children’s Hospital Colorado, Aurora, CO 80045, USA; Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045, USA
Eric Prince
Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children’s Hospital Colorado, Aurora, CO 80045, USA; Department of Neurosurgery, University of Colorado Denver, Aurora, CO 80045, USA
Bridget Sanford
Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045, USA
Todd C. Hankinson
Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children’s Hospital Colorado, Aurora, CO 80045, USA; Department of Neurosurgery, University of Colorado Denver, Aurora, CO 80045, USA
Michael H. Handler
Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children’s Hospital Colorado, Aurora, CO 80045, USA; Department of Neurosurgery, University of Colorado Denver, Aurora, CO 80045, USA
Rajeev Vibhakar
Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children’s Hospital Colorado, Aurora, CO 80045, USA; Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045, USA
Ken L. Jones
Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045, USA
Siddhartha Mitra
Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children’s Hospital Colorado, Aurora, CO 80045, USA; Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045, USA
Jay R. Hesselberth
RNA Biosciences Initiative, University of Colorado Denver, Aurora, CO 80045, USA
Nicholas K. Foreman
Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children’s Hospital Colorado, Aurora, CO 80045, USA; Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045, USA; Department of Neurosurgery, University of Colorado Denver, Aurora, CO 80045, USA
Andrew M. Donson
Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children’s Hospital Colorado, Aurora, CO 80045, USA; Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045, USA; Corresponding author
Summary: Ependymoma (EPN) is a brain tumor commonly presenting in childhood that remains fatal in most children. Intra-tumoral cellular heterogeneity in bulk-tumor samples significantly confounds our understanding of EPN biology, impeding development of effective therapy. We, therefore, use single-cell RNA sequencing, histology, and deconvolution to catalog cellular heterogeneity of the major childhood EPN subgroups. Analysis of PFA subgroup EPN reveals evidence of an undifferentiated progenitor subpopulation that either differentiates into subpopulations with ependymal cell characteristics or transitions into a mesenchymal subpopulation. Histological analysis reveals that progenitor and mesenchymal subpopulations co-localize in peri-necrotic zones. In conflict with current classification paradigms, relative PFA subpopulation proportions are shown to determine bulk-tumor-assigned subgroups. We provide an interactive online resource that facilitates exploration of the EPN single-cell dataset. This atlas of EPN cellular heterogeneity increases understanding of EPN biology.
