Evidence mapPaperPMID 41963569Full record

ArticleFunctional & integrative genomics2026

Single-cell and spatial transcriptomics reveal TNF-α promotes glioblastoma proliferation and migration via CP-mediated KLF10 upregulation.

Jiasheng Zhong, Zechuan Peng, Hongyi Cai, Yunhe Zhao, Liya Ma, Yiquan Ke, Xinlin Sun

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Article in Functional & integrative genomics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

7 authors.

Jiasheng ZhongDepartment of Neurosurgery, Second Clinical Medical College of Southern Medical University, Zhujiang Hospital, Guangzhou, China.
Zechuan PengDepartment of Neurosurgery, Second Clinical Medical College of Southern Medical University, Zhujiang Hospital, Guangzhou, China.
Hongyi CaiDepartment of Physiology, Shantou University Medical College, Shantou, 515041, Guangdong Province, People's Republic of China.
Yunhe ZhaoDepartment of Neurosurgery, Second Clinical Medical College of Southern Medical University, Zhujiang Hospital, Guangzhou, China.
Liya MaDepartment of Neurosurgery, Second Clinical Medical College of Southern Medical University, Zhujiang Hospital, Guangzhou, China.
Yiquan KeDepartment of Neurosurgery, Second Clinical Medical College of Southern Medical University, Zhujiang Hospital, Guangzhou, China. kyquan@smu.edu.cn.
Xinlin SunDepartment of Neurosurgery, Second Clinical Medical College of Southern Medical University, Zhujiang Hospital, Guangzhou, China. remmusxl@smu.edu.cn.

Funding

the National Natural Science Foundation of China No. 82403646
6 · The paper itself

Abstract

Glioblastoma is a highly aggressive brain tumor characterized by substantial intratumoral heterogeneity and poor clinical outcomes. Understanding the transcriptional programs and microenvironmental cues that drive aggressive tumor cell states is essential for developing targeted therapies. We integrated bulk and single-cell RNA-seq data from TCGA, CGGA, and published spatial datasets. Using BayesPrism deconvolution, we identified a glioblastoma subpopulation (G1) whose abundance consistently correlated with poor prognosis. Pseudotime analysis with Monocle2 positioned G1 at the terminal state of malignant differentiation. To uncover regulatory mechanisms, we applied NetAct and SCENIC, which highlighted KLF10 as a key transcription factor. Spatial transcriptomic deconvolution and NicheNet analysis suggest that microenvironment-derived TNF likely drives G1 transition via FAT1/TNFRSF1A and ceruloplasmin (CP) induction. Functional experiments including CCK-8, EdU, Transwell, and wound healing assays validated the TNF/CP/KLF10 axis as a driver of glioblastoma cell proliferation and migration. Among the eight glioma cell subtypes identified, the G1 subtype was consistently associated with poor prognosis and showed higher proliferation and migration scores. G1 cells showed enhanced ER stress signaling. Integrated analysis identified TNF-α as a key ligand secreted by cDCs, macrophages, and microglia within G1-enriched spatial niches. FAT1 and TNFRSF1A were identified as G1-specific TNF receptors. Transcription factor KLF10 was identified as a master regulator of G1 identity. Functional assays demonstrated that TNF-α promotes glioblastoma cell proliferation and migration through a CP/KLF10 axis, wherein TNF-α-induced CP upregulation modulates KLF10 expression, and these biological effects were reversed by CP suppression. Our study defines a malignant glioblastoma cell state (G1) regulated by intrinsic transcriptional programs and extrinsic immune-derived TNF–CP signaling. Targeting the G1 program or interrupting the TNF-α/CP/KLF10 axis may offer new therapeutic strategies for glioblastoma.

Indexed as

Brain NeoplasmsEarly Growth Response Transcription FactorsGlioblastomaKruppel-Like Transcription FactorsTumor Necrosis Factor-alphaCadherinsCell Line, TumorCell MovementCell ProliferationGene Expression Regulation, NeoplasticHumansReceptors, Tumor Necrosis Factor, Type ISpatial TranscriptomicsUp-RegulationCadherinsEarly Growth Response Transcription FactorsFAT1 protein, humanKLF10 protein, humanKruppel-Like Transcription FactorsReceptors, Tumor Necrosis Factor, Type ITumor Necrosis Factor-alphaCeruloplasmin (CP)GlioblastomaIntratumoral heterogeneityKLF10Single-cell RNA sequencingTNF-α signaling

Identifiers

PMID41963569

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.