Details

Autor(en) / Beteiligte

• Gillen, Austin E.
• Riemondy, Kent A.
• Amani, Vladimir
• Griesinger, Andrea M.
• Gilani, Ahmed
• Venkataraman, Sujatha
• Madhavan, Krishna
• Prince, Eric
• Sanford, Bridget
• Hankinson, Todd C.
• Handler, Michael H.
• Vibhakar, Rajeev
• Jones, Ken L.
• Mitra, Siddhartha
• Hesselberth, Jay R.
• Foreman, Nicholas K.
• Donson, Andrew M.

Titel

Single-Cell RNA Sequencing of Childhood Ependymoma Reveals Neoplastic Cell Subpopulations That Impact Molecular Classification and Etiology

Ist Teil von

• Cell reports (Cambridge), 2020-08, Vol.32 (6), p.108023-108023, Article 108023

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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. [Display omitted] •Characterization and interactive browser of ependymoma single cells•Identification of progenitor, ependyma-differentiated, and mesenchymal cell types•Subpopulation proportions influence bulk-tumor transcriptomic molecular subgrouping•Progenitor and mesenchymal subpopulations co-localize in peri-necrotic zones Gillen et al. use scRNA-seq to reveal diverse neoplastic subpopulations that underlie the bulk-tumor molecular subgrouping schema in childhood ependymoma. They identify potential divergent lineage trajectories that are driven by either developmental or hypoxic stimuli. This resource facilitates a more accurate interpretation of complex childhood ependymoma biological data.