SC-33 * POLYCOMB GROUP PROTEIN Bmi1 CONTROLS NEURAL STEM AND PROGENITOR CELL MAINTENANCE AND GLIOBLASTOMA TUMOUR DEVELOPMENT
Bibliographic record
Abstract
Bmi1, a polycomb group protein is required for self-renewal of neural stem and progenitor cells (NSPCs). Elevated Bmi1 expression is observed in most brain tumours, including glioblastoma (GBM). GBM, one of the most aggressive and heterogeneous tumours is known to possess a subpopulation of brain tumour initiating cells (BTICs) that have acquired stem cell properties and are exclusively capable of driving tumour formation in a human-mouse xenograft model. These observations raise the question of whether over-expressing Bmi1 is sufficient to promote self-renewal or tumorigenesis by NSPCs and whether loss of Bmi1 in GBM BTICs affects the progression of brain tumours. Using lentiviral constructs, we studied the gain of Bmi1 in human NSPCs and observed increased self-renewal and proliferative capacity of these cells. Subsequently, OEBmi1 NSPCs were injected in NOD-SCID mouse brains to assess their tumorigenic ability. Furthermore, knockdown of Bmi1 was performed in human GBM BTICs, which resulted in inhibition of clonogenic potential in vitro as well as decreased tumour cell mass in vivo. Lastly, to determine the comprehensive Bmi1 transcriptional network in human NSPCs and GBM BTICs, we applied ChIP-seq strategy to discover if Bmi1 binds to the promoter region of genes critical for neural lineage commitment and if these genes are involved in brain tumour formation. Together with RNA-seq data from human NSPCs and GBM BTICs sorted for stem cell marker CD133, this data will generate a comprehensive genome-wide Bmi1 binding profile and identify critical downstream Bmi1 targets & signaling pathways important for brain tumour maintenance.
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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 | 0.000 |
| 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".