{"id":"doi:10.1038/s41467-023-36707-6","kind":"article","title":"Spatial transcriptomics reveals niche-specific enrichment and vulnerabilities of radial glial stem-like cells in malignant gliomas","authors":["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"],"author_count":28,"year":2023,"published":"2023-02-23","venue":"Nature communications","cited_by":213,"doi":"10.1038/s41467-023-36707-6","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41467-023-36707-6","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41467-023-36707-6","updated":null,"pmid":"36823172","pmcid":"PMC9950149","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC9950149/pdf","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_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Spatial transcriptomics reveals niche-specific enrichment and vulnerabilities of radial glial stem-like cells in malignant gliomas\" by Ren Y, Huang Z, Zhou L et al., https://doi.org/10.1038/s41467-023-36707-6, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"single-cell-spatial","name":"Single-Cell & Spatial Omics","domain_slug":"biotech"}],"cited_in_dossiers":[]}