Medulloblastoma Spatial Transcriptomics Reveals Tumor Microenvironment Heterogeneity With High-Density Progenitor Cell Regions Correlating With High-Risk Disease.
5 affiliations
- 1Department of Pediatrics, Emory School of Medicine, Atlanta, GA.
- 2Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA.
- 3Department of Pathology, NYU Langone Health and Grossman School of Medicine, New York, NY.
- 4Department of Pathology and Laboratory Medicine, Children's Healthcare of Atlanta and Emory School of Medicine, Atlanta, GA.
- 5Department of Biomedical Engineering, Emory University, Atlanta, GA.
Abstract
Purpose
No curative options are available for medulloblastoma (MB) in the relapse setting. The tumor microenvironment (TME) influences progression and therapy response, presenting a promising target for therapeutic advances. Prior single-cell analyses have characterized the cellular components of the TME but lack spatial context. We hypothesize that spatial architecture, beyond cell composition, influences tumor progression and treatment outcomes.Methods
We performed spatial transcriptomic sequencing on 18 pediatric MB samples obtained at diagnosis, including two matched diagnosis-relapse pairs. Samples at diagnosis were stratified into high- and standard-risk groups. Spatial data were analyzed for spatial proximity to other cell types, cell-cell communication networks, and expression of cell cycle dormancy signatures. Findings were validated using immunohistochemistry in the same cohort.Results
Our analyses revealed intertumoral and intratumoral heterogeneity within the TME, comprising tumor-associated astrocytes (TAAs), macrophages (TAMs), stromal components, and distinct subpopulations of MB cells at different stages of neuronal differentiation and cell cycle progression. We identified dense regions of quiescent progenitor-like MB cells enriched in patients with high-risk (HR) features and an increase in TAAs, TAMs, and dysregulated vascular endothelium following relapse.Conclusion
Our study presents novel insights into the spatial architecture and cellular landscape of the MB-TME, highlighting differential spatial patterns correlating with HR features. Future studies should evaluate their role in relapse and therapy resistance and may lead to uncovering novel therapeutic targets.
Related
- Mapping intestinal microenvironment heterogeneity in Hirschsprung's disease by spatial transcriptomics: Role of THBS1 in macrophage polarization and neural stem cell regulation.
- Integrated immunopeptidomics and transcriptomics reveal a cancer-restricted non-canonical HLA class I ligandome in medulloblastoma
- The neuronal plasticity gene CRTC1 links survival with mitochondrial programs and tumor microenvironment features in Group 3 β medulloblastoma
- The Role of Spatial Transcriptomics in Exploring the Tumor Microenvironment in Neuroblastoma
- Single-cell transcriptomics-based analysis of cellular heterogeneity in aggrephagy in gastric cancer and development of a prognostic model
BibTeX
@article{chien2026medulloblastoma,
title = {{Medulloblastoma Spatial Transcriptomics Reveals Tumor Microenvironment Heterogeneity With High-Density Progenitor Cell Regions Correlating With High-Risk Disease.}},
author = {Franklin Chien and Marina E Michaud and Mojtaba Bakhtiari and Chanel Schroff and Matija Snuderl and Jose E Velazquez Vega and Tobey J MacDonald and Manoj K Bhasin},
journal = {JCO precision oncology},
year = {2026},
month = oct,
doi = {10.1200/po-25-01195},
url = {https://europepmc.org/article/MED/42868339},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Medulloblastoma Spatial Transcriptomics Reveals Tumor Microenvironment Heterogeneity With High-Density Progenitor Cell Regions Correlating With High-Risk Disease.
AU - Franklin Chien
AU - Marina E Michaud
AU - Mojtaba Bakhtiari
AU - Chanel Schroff
AU - Matija Snuderl
AU - Jose E Velazquez Vega
AU - Tobey J MacDonald
AU - Manoj K Bhasin
PY - 2026
DA - 2026/10/13
JO - JCO precision oncology
DO - 10.1200/po-25-01195
UR - https://europepmc.org/article/MED/42868339
AB - Purpose No curative options are available for medulloblastoma (MB) in the relapse setting. The tumor microenvironment (TME) influences progression and therapy response, presenting a promising target for therapeutic advances. Prior single-cell analyses have characterized the cellular components of the TME but lack spatial context. We hypothesize that spatial architecture, beyond cell composition, influences tumor progression and treatment outcomes.Methods We performed spatial transcriptomic sequencing on 18 pediatric MB samples obtained at diagnosis, including two matched diagnosis-relapse pairs. Samples at diagnosis were stratified into high- and standard-risk groups. Spatial data were analyzed for spatial proximity to other cell types, cell-cell communication networks, and expression of cell cycle dormancy signatures. Findings were validated using immunohistochemistry in the same cohort.Results Our analyses revealed intertumoral and intratumoral heterogeneity within the TME, comprising tumor-associated astrocytes (TAAs), macrophages (TAMs), stromal components, and distinct subpopulations of MB cells at different stages of neuronal differentiation and cell cycle progression. We identified dense regions of quiescent progenitor-like MB cells enriched in patients with high-risk (HR) features and an increase in TAAs, TAMs, and dysregulated vascular endothelium following relapse.Conclusion Our study presents novel insights into the spatial architecture and cellular landscape of the MB-TME, highlighting differential spatial patterns correlating with HR features. Future studies should evaluate their role in relapse and therapy resistance and may lead to uncovering novel therapeutic targets.
SN - 2473-4284
ER -