# Spatial transcriptomics reveals niche-specific enrichment and vulnerabilities of radial glial stem-like cells in malignant gliomas

Article · Ren Y, Huang Z, Zhou L, Xiao P, Song J, He P, Xie C, Zhou R, Li M, Dong X, Mao Q, You C, Xu J, Liu Y, Lan Z, Zhang T, Gan Q, Yang Y, Chen T, Huang B, Yang X, Xiao A, Ou Y, Su Z, Chen L and 3 more

- Archive id: doi:10.1038/s41467-023-36707-6
- Published: 2023-02-23
- Venue: Nature communications
- DOI: https://doi.org/10.1038/s41467-023-36707-6
- PMID: 36823172
- PMCID: PMC9950149
- Citations: 213
- Source URL: https://doi.org/10.1038/s41467-023-36707-6
- PDF: https://europepmc.org/articles/PMC9950149/pdf
- Provenance: europepmc

## Abstract

Diffuse midline glioma-H3K27M mutant (DMG) and glioblastoma (GBM) are the most lethal brain tumors that primarily occur in pediatric and adult patients, respectively. Both tumors exhibit significant heterogeneity, shaped by distinct genetic/epigenetic drivers, transcriptional programs including RNA splicing, and microenvironmental cues in glioma niches. However, the spatial organization of cellular states and niche-specific regulatory programs remain to be investigated. Here, we perform a spatial profiling of DMG and GBM combining short- and long-read spatial transcriptomics, and single-cell transcriptomic datasets. We identify clinically relevant transcriptional programs, RNA isoform diversity, and multi-cellular ecosystems across different glioma niches. We find that while the tumor core enriches for oligodendrocyte precursor-like cells, radial glial stem-like (RG-like) cells are enriched in the neuron-rich invasive niche in both DMG and GBM. Further, we identify niche-specific regulatory programs for RG-like cells, and functionally confirm that FAM20C mediates invasive growth of RG-like cells in a neuron-rich microenvironment in a human neural stem cell derived orthotopic DMG model. Together, our results provide a blueprint for understanding the spatial architecture and niche-specific vulnerabilities of DMG and GBM.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Single-Cell & Spatial Omics](https://space-kitty.com/topics/single-cell-spatial)

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