A longitudinal single-cell and spatial multiomic atlas of pediatric high-grade glioma

作者：Jonathan Sussman, Derek A. Oldridge, Wenbao Yu, Chia‐Hui Chen, Abigail M. Zellmer, Jiazhen Rong, Arianne Parvaresh-Rizi, Anusha Thadi, Austin Yang, Joseph S. Tumulty, Barbara Xiong, David Wu, Yusha Sun, Shovik Bandyopadhyay, Jason Z. Xu, Stephanie Nicole Brosius, Una Yamamoto Barkardottir, Isabelle Seka, Kyung Jin Ahn, Omar Elghawy, Amy E. Baxter, Mateusz Koptyra, Rami Sesha Vanguri, Stephanie B McGrory, Phillip B. Storm, Nduka Amankulor, Mariarita Santi, Angela Nicole Viaene, Nancy R. Zhang, Thomas De Raedt, Kristina Ann Cole, Kai Tan · 发表于：Cell Reports Medicine · 年份：2026 · DOI：10.1016/j.xcrm.2026.102766 · 被引用次数：9 · 研究领域：Single-cell and spatial transcriptomics、Glioma Diagnosis and Treatment、Immune cells in cancer

Pediatric high-grade glioma (pHGG) is an incurable central nervous system malignancy that is a leading cause of pediatric cancer death. While pHGG shares many similarities with adult glioma, it comprises distinct disease entities. In this study, we longitudinally profile a molecularly diverse cohort of 16 pHGG patients through single-nucleus RNA and ATAC sequencing, whole-genome sequencing, and CODEX spatial proteomics to capture the evolution of neoplastic and microenvironmental features during disease progression and treatment. We define a set of core pHGG neoplastic cell states and observe differential tumor-myeloid interactions between malignant cell phenotypes. We find that essential neuromodulators and the interferon response are upregulated post-therapy, implicating them as malignant cell-intrinsic targets. We observe an increase in oligodendrocytes upon progression and that they coordinate spatial motifs with proneural tumor cells. This multiomic atlas of longitudinal pHGG captures features of therapy response and provides a scalable reference for the study of pediatric brain tumors.