Review Article

From single-cell snapshots to spatial panoramas – a holistic multiomics map of glioblastoma

¹ Department of Oncology, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150080, China
² Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Stockholm, 14152, Sweden
³ Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, 00014, Finland
⁴ Wihuri Research Institute, Helsinki, 00270, Finland

^* Corresponding authors: This email address is being protected from spambots. You need JavaScript enabled to view it. (Yizhou Hu), This email address is being protected from spambots. You need JavaScript enabled to view it. (Li Li)

Received: 19 August 2025
Accepted: 29 October 2025

Abstract

Single-cell studies have replaced bulk TCGA “subtypes” with a dynamic model in which multiple malignant programs interconvert in glioblastoma, and the balance among these programs is shaped by genetic lesions and local ecological cues. These programmes mirror distorted developmental gene programmes, and their intrinsic developmental plasticity fuels state switching and therapeutic escape. Spatial multi-omics now anchors these programs to anatomy, revealing a reproducible, hypoxia-graded five-layer architecture from necrotic core to infiltrative rim and identifying hypoxia as a long-range organizer. Whole-tumour 3D sampling links clonal evolution to territory, showing that early driver events can span the lesion, while later changes remain regionally restricted. This geography-aware view helps explain why single agents often fail and points to niche-targeted combinations and delivery strategies tailored to the blood-tumour barrier states. We outline how an integrated, spatially resolved multi-omics atlas can guide compartment-specific therapy and prospective monitoring in precision neuro-oncology.