Integrated single-cell transcriptomic analyses reveal that GPNMB-high macrophages promote PN-MES transition and impede T cell activation in GBM.
IF: 11.205
Cited by: 4


Glioblastoma (GBM) is the most aggressive type of primary brain tumor and is often resistant to current therapies. Tumor microenvironment-centered therapies may unleash new hope for GBM treatment. Therefore, an in-depth understanding of tumor-stroma communication is urgently needed to identify promising therapeutic targets. We systematically analyzed GBM single-cell RNA sequencing (scRNA-seq), bulk RNA-seq and spatial scRNA-seq data from various human and mice studies to characterize the network within the microenvironment. Moreover, we applied ex vivo co-culture system, flow cytometry analysis and immunofluorescent staining to validate our findings. Our integrative analyses revealed that highly heterogeneous GBM tumor cells can be classified into MES-like, AC-like, OPC-like and NPC-like subtypes based on molecular studying. Additionally, trajectory and regulatory network inference implied a PN to MES cell state transition regulated by specific transcriptional factor (TF) regulons. Importantly, we discovered that glycoprotein nonmetastatic B (GPNMB) derived from macrophages played a crucial role in this transition through immune cell-tumor interplay. Besides, through deep signal transduction analyses and cell co-culture studies, we further disclosed that these GPNMB-high macrophage subpopulations, originating from monocytes, could also ineffectively retain T cells from activating by dendritic cells (DCs). Our study suggests that targeting this particular GPNMB-high macrophage subset may provide a new strategy to control GBM plasticity and facilitate T cell-based immunotherapy. A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.


Glycoprotein NMB
Integrated analysis
Single cell

MeSH terms

Brain Neoplasms
Eye Proteins
Membrane Glycoproteins
Single-Cell Analysis
Tumor Microenvironment


Xiong, Aizhen
Zhang, Jiwei
Chen, Yan
Zhang, Yi
Yang, Fan