ANGI-11. MESENCHYMAL STEM CELLS AND PERIVASCULAR STROMA ARE ASSOCIATED WITH MICROVASCULAR PROLIFERATION, IMMUNOSUPPRESSION, AND POOR OUTCOME IN GLIOMA
Bibliographic record
Abstract
Abstract INTRODUCTION Microvascular proliferation (MVP) is a hallmark of glioblastoma (GBM) and other World Health Organization (WHO) grade 4 gliomas. MVP is also a poor prognostic marker in various solid tumors. Despite its clinical importance, the biological underpinnings of MVP are controversial and remain unclear, especially at the single cell level. METHODS In this study, we perform single cell RNA-sequencing (scRNA-seq) on paired CD45-CD105+ vascular/perivascular stromal cells (PVSCs) and CD45+CD105± immune cells from 16 primary glioma patient samples (7 glioblastomas, 4 astrocytomas, and 5 oligodendrogliomas for a total of 76,141 cells), both with and without MVP. scRNA-seq was complemented with spatial transcriptomic and multiplex immunofluorescence assays. RESULTS These analyses revealed the presence of developmentally-related mesenchymal stem cells (MSCs) alongside cancer-associated fibroblasts (CAFs), pericytes, fibromyocytes, and smooth muscle cells within the CD45-CD105+ compartment. RNA velocity (trajectory) analysis identified PDGFRB as a putative driver gene guiding MSCs towards more mature PVSCs. Signaling network analyses and digital spatial profiling uncovered interactions between PDGFRB+ PVSCs and immunosuppressive myeloid cell subsets enriched in the perivascular niche, suggesting targetable receptor-ligand interactions. Additionally, a gene signature of MVP-associated PVSCs predicted worse prognosis in glioma and multiple other solid tumors. DISCUSSION This study provides a novel transcriptomic cell atlas of PVSCs and immune cells in glioma, helping to refine the biological model of MVP which has traditionally focused on endothelial cells. PDGFRβ+ PVSC-associated MVP is linked to immunosuppression, offering a chance for exploitation via PDGFRβ inhibitors. Furthermore, our data suggests MSCs, potentially from the periphery, may play a role colonizing the glioma perivascular niche and contributes to MVP, supporting future investigation of systemic treatments.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".