Single cell spatial analysis identifies regulators of brain tumor initiating cells
Bibliographic record
Abstract
Abstract Glioblastomas (GBMs) are aggressive brain tumors with extensive intratumoral heterogeneity. Here, we used spatial transcriptomics and single-cell ATAC-seq to dissect the transcriptome of distinct anatomical regions of the tumor microenvironment. We identified numerous extracellular matrix (ECM) molecules including biglycan elevated in areas infiltrated with brain tumor-initiating cells (BTICs). Single-cell RNA sequencing showed that the ECM molecules were differentially expressed by cells including injury response versus developmental BTICs. Exogeneous biglycan or overexpression of biglycan resulted in a higher proliferation rate of BTICs, and this was associated mechanistically with LDL receptor-related protein 6 (LRP6) binding and activation of the Wnt/β-catenin pathway. Biglycan-overexpressing BTICs grew to a larger tumor mass when implanted intracranially in mice. This study points to the spatial heterogeneity of ECM molecules in the GBM microenvironment and suggests biglycan-LRP6 axis as a therapeutic target to curb GBM growth.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| 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".