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

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…

• NN
  National Natural Science Foundation of China

  Awards: 2017YFA0106500, 82173179, 82273117, 31871376
• SU
  Sichuan University

  Award: ZYYC20019
• CS
  Chengdu Science and Technology Bureau
• NK
  National Key Research and Development Program of China

  Awards: 2022YFA1105200, 2017YFA0106800, 2017YFA0106500
• NK
  National Key Research and Development Program of China Stem Cell and Translational Research

  Awards: 2017YFA0106800, 2022YFA1105200, 2017YFA0106500
• WC
  West China Hospital, Sichuan University