Microglia-Derived Brain Macrophages Associate with Glioblastoma Stem Cells: A Potential Mechanism for Tumor Progression Revealed by AI-Assisted Analysis
Abstract
1. Introduction
2. Materials and Methods
2.1. Wet Laboratory Work
2.2. The PathoFusion Framework
2.3. Dataset Preparation, Partitioning, Filtering, and Thresholding for CD276, Iba1, and CD163 Immunoreactive Cell Analysis
2.4. Post-Processing Steps
3. Results
3.1. Morphological Tissue Analysis Is Greatly Aided by AI Assistance
3.2. The PathoFusion Framework Allows Visualization of the Locations of GSCs and Microglia/Macrophages on the Basis of Multimodal Heatmaps
3.3. Fusion Heatmaps Reveal Regional Differences Between the Localization of CD276+ GSCs and Iba1+ and CD163+ Macrophages
3.4. Comparative Analysis of the Multimodal Heatmaps Indicates That Microglia-Derived Brain Macrophages Are More Frequently Associated with Glioblastoma Stem Cells than Myeloid Cells
4. Discussion
4.1. Molecular Similarities Between GSCs and NSCs
4.2. Co-Localization of Microglia-Derived Brain Macrophages and NSCs Is a Normal Feature of the SVZ
4.3. Microglia That Reside in Close Proximity to NSCs in the SVZ Are Characterized by a More Amoeboid Morphology
4.4. GSCs May Enhance the Expression of CD163 in Tumor-Associated Macrophages
4.5. CD163-Expressing Macrophages Promote the Self-Renewal and Maintenance of GSCs
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Case | Sex | Age at Diagnosis | Survival (Months) | Localization |
---|---|---|---|---|
1 * | F | 62 | 16 | Right occipital |
2 * | M | 55 | 14 | Left occipital, parietal |
3 * | F | 46 | 10 | Left frontal |
4 * | M | 70 | 4 | Right frontal |
5 | F | 54 | 95 | Left parietal |
6 | M | 33 | 15 | Right frontal |
7 * | F | 57 | 4 | Right frontotemporal |
8 | F | 48 | 27 | Right frontal, occipital, parietal, temporal |
9 * | M | 65 | 14 | Right frontal |
10 * | M | 69 | 16 | Right frontal |
11 | M | 51 | 23 | Left parietal |
12 * | F | 55 | 12 | Left frontal |
13 | F | 85 | 4 | Left temporal |
14 | F | 72 | 13 | Right temporal |
15 * | M | 77 | 20 | Right parietal |
16 1 | M | 33 | 15 | Right frontal |
17 | F | 51 | Unknown | Right frontal |
18 | M | 50 | 16 | Left temporal |
19 | F | 60 | 20 | Right temporal |
20 | F | 75 | 27 | Right frontal |
21 * | M | 65 | 10 | Left temporal |
22 | M | 33 | 8 | Right frontal |
23 | F | 60 | 21 | Left temporal |
24 | M | 68 | 10 | Left frontal |
25 | F | 59 | 38 | Right occipital |
26 * | F | 79 | 12 | Right parietal |
27 | M | 73 | 17 | Right frontal |
28 * | M | 50 | 20 | Right parietal |
29 * | M | 66 | 12 | Right parietal |
30 * | M | 50 | 15 | Right temporal |
31 | M | 78 | 5 | Right frontal |
32 | F | 60 | 15 | Right occipital |
33 * | M | 75 | 16 | Right occipital |
34 | F | 62 | 13 | Right occipital, parietal |
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Zheng, Y.; Fuse, H.; Alzoubi, I.; Graeber, M.B. Microglia-Derived Brain Macrophages Associate with Glioblastoma Stem Cells: A Potential Mechanism for Tumor Progression Revealed by AI-Assisted Analysis. Cells 2025, 14, 413. https://doi.org/10.3390/cells14060413
Zheng Y, Fuse H, Alzoubi I, Graeber MB. Microglia-Derived Brain Macrophages Associate with Glioblastoma Stem Cells: A Potential Mechanism for Tumor Progression Revealed by AI-Assisted Analysis. Cells. 2025; 14(6):413. https://doi.org/10.3390/cells14060413
Chicago/Turabian StyleZheng, Yuqi, Haneya Fuse, Islam Alzoubi, and Manuel B. Graeber. 2025. "Microglia-Derived Brain Macrophages Associate with Glioblastoma Stem Cells: A Potential Mechanism for Tumor Progression Revealed by AI-Assisted Analysis" Cells 14, no. 6: 413. https://doi.org/10.3390/cells14060413
APA StyleZheng, Y., Fuse, H., Alzoubi, I., & Graeber, M. B. (2025). Microglia-Derived Brain Macrophages Associate with Glioblastoma Stem Cells: A Potential Mechanism for Tumor Progression Revealed by AI-Assisted Analysis. Cells, 14(6), 413. https://doi.org/10.3390/cells14060413