36 ISOLATION OF CANDIDATE GLIOBLASTOMA-INITIATING CELLS FROM MULTIPLE REGIONS OF THE ADULT MAMMALIAN BRAIN USING PLATELET-DERIVED GROWTH FACTOR C
Bibliographic record
Abstract
Abstract Brain Cancer Canada Travel Award Recipient An important observation in neurobiology was the discovery of neural stem cells (NSCs) in the adult mammalian brain by Reynolds and Weiss. Although ‘brain repair’ was the initial thrust of research that followed this observation, the enduring contribution may lie in neuro-oncology where dormant stem cells in the adult brain are thought to be the cells-of-origin of GBM. The idea that ‘remnants’ of the developing brain give rise to lethal cancers years later is fascinating but difficult to study without a model system. The current method for culturing NSCs from the stem cell-rich subventricular zone (SVZ) relies on media supplemented with Epidermal Growth Factor and Fibroblast Growth Factor (EGF/FGF). These cells can be maintained indefinitely but are proliferative, unlike how origin-specific stem cells behave. Furthermore, most GBMs arise in normal-appearing brain, not from expanding masses of non-cancerous stem cells. Here, we show that quiescent NSCs can be isolated from the SVZ and cerebral cortex of adult mice using Platelet-Derived Growth Factor C (PDGFC). These SOX2/Nestin positive cells grow in small minimally enlarging spheres and are capable of multi-lineage differentiation, can expand in EGF/FGF, and transition to oligodendrocyte progenitor cells in PGDFC+FGF. Gene expression analysis reveals that NSCs harvested using PDGFC are similar to NSCs in EGF/FGF, but based on an analysis of quiescence genes, are more like SVZ tissue thanNSCs in EGF/FGF. We are testing whether P53 null NSCs isolated in PDGFC then switched to PDGFA become growth factor-independent GBM-like cells (Bohm et al., 2020).
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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 | 0.000 | 0.001 |
| 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".