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- Title
Spatial transcriptomics reveals niche-specific enrichment and vulnerabilities of radial glial stem-like cells in malignant gliomas.
- Authors
Ren, Yanming; Huang, Zongyao; Zhou, Lingling; Xiao, Peng; Song, Junwei; He, Ping; Xie, Chuanxing; Zhou, Ran; Li, Menghan; Dong, Xiangqun; Mao, Qing; You, Chao; Xu, Jianguo; Liu, Yanhui; Lan, Zhigang; Zhang, Tiejun; Gan, Qi; Yang, Yuan; Chen, Tengyun; Huang, Bowen
- 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. The spatial organisation of diffuse midline glioma-H3K27M mutant (DMG) and glioblastoma (GBM) remains to be investigated. Here, the authors integrate short-read and long-read spatial profiling of DMG and GBM to identify regulatory programs and cellular ecosystems in distinct glioma niches.
- Subjects
NEUROGLIA; CANCER cells; GLIOMAS; BRAIN tumors; NEURAL stem cells; HUMAN stem cells
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-36707-6