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Multidimensional profiling of heterogeneity in supratentorial ependymomas
Daeun Jeong1,2, Sara G Danielli1,2, Kendra K Maaß3,4
1Department of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
Nature
|March 12, 2026
Summary
Supratentorial ependymomas, aggressive childhood brain tumors, exhibit distinct progenitor cell states resembling early brain development. Understanding these states and tumor organization is crucial for potential therapeutic strategies.
Area of Science:
- Neuro-oncology
- Developmental Biology
- Cancer Research
Background:
- Supratentorial ependymomas are aggressive pediatric brain tumors with diverse molecular and clinical subgroups.
- The developmental origins and microenvironmental influences driving tumor cell transformation remain poorly understood.
Purpose of the Study:
- To define supratentorial ependymoma cell states, spatial organization, and behavior within the neural microenvironment.
- To integrate transcriptional and phenotypic data for a comprehensive understanding of tumor heterogeneity.
Main Methods:
- Integrated single-cell and spatial transcriptomics.
- Utilized in vitro and in vivo live-cell imaging.
- Analyzed tumor cell states, spatial architecture, and interactions within the microenvironment.
Main Results:
- Identified two progenitor-like cell states (neuroepithelial-like and embryonic-like) mirroring early human brain development.
- Revealed distinct spatial organization patterns influenced by mesenchymal and hypoxia signatures.
- Demonstrated brain-resident cells promoting neuronal-like cell phenotypes and migratory behaviors.
Conclusions:
- Supratentorial ependymomas exhibit complex cellular heterogeneity with developmental roots.
- Spatial organization and microenvironment interactions significantly influence tumor behavior.
- Findings offer a multidimensional framework for understanding tumor heterogeneity and potential clinical implications.
