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Related Experiment Video

Updated: Apr 8, 2026

Modeling Astrocytoma Pathogenesis In Vitro and In Vivo Using Cortical Astrocytes or Neural Stem Cells from Conditional, Genetically Engineered Mice
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Single-Cell and Bulk Transcriptomic Integration Reveals a Stemness-Related Astrocyte Subpopulation for Prognostic

Jiachong Wang1, Jiale Li2, Chunyuan Zhang3,4

  • 1Department of Neurosurgery, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou City, Hainan Province, 570208, China.

Current Medicinal Chemistry
|April 7, 2026
PubMed
Summary

A new four-gene signature identifies stemness-related astrocytes in glioblastoma (GBM). This prognostic tool stratifies patients and reveals an immunosuppressive tumor microenvironment, guiding targeted therapy for aggressive brain tumors.

Keywords:
Glioblastomaastrocytes.prognostic modelsingle-cell RNA sequencingstemnesstumor microenvironment

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Area of Science:

  • Oncology
  • Genomics
  • Molecular Biology

Background:

  • Glioblastoma (GBM) is a highly aggressive brain tumor characterized by significant cellular heterogeneity.
  • Stemness-related cell subpopulations are implicated in GBM progression and resistance to therapy, but their prognostic significance is not fully understood.

Purpose of the Study:

  • To identify and characterize stemness-associated astrocyte subpopulations in GBM.
  • To develop a prognostic risk model based on a stemness-related gene signature.
  • To investigate the relationship between the identified signature, tumor microenvironment, and clinical outcomes.

Main Methods:

  • Integration of single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data to identify a stemness-high astrocyte subpopulation.
  • Construction and validation of a four-gene prognostic risk model using LASSO Cox regression in TCGA and CGGA cohorts.
  • In vitro functional assays and analyses of tumor microenvironment and associated pathways.

Main Results:

  • A four-gene signature (ALDOA, FABP5, TIMP1, MT1M) was established, robustly stratifying GBM patients into high- and low-risk groups with distinct overall survival.
  • The risk score served as an independent prognostic factor, outperforming age and IDH mutation status.
  • High-risk tumors exhibited an immunosuppressive microenvironment with increased immune/stromal scores and activated stemness-related pathways.

Conclusions:

  • A stemness-associated four-gene signature was identified in GBM, providing an independent prognostic tool.
  • This signature reflects immune microenvironment remodeling and aids in risk stratification.
  • The findings offer insights into potential targeted therapies for GBM.