CSIG-15. CIC REGULATES NEURAL STEM/PROGENITOR PROLIFERATION AND DIFFERENTIATION
Bibliographic record
Abstract
Capicua (Cic) is an evolutionarily conserved HMG box-containing transcriptional repressor. Mutations in the CIC gene (encoded on human chr 19q) have been found in a diverse range of human cancers, but are most striking in their association with oligodendrogliomas (ODGs), where tumor cells bear resemblance to immature oligodendrocytes or OPCs. CIC mutations are present in two thirds of ODGs and occur in the setting of concurrent 1p/19q loss and IDH1/2 mutation. Although its link to ODGs is established, little is known of the role that Cic plays during normal cortical development or how its loss may contribute to gliomagenesis. Here, we examine the relationship between CIC expression and cell identity in the developing mouse brain and begin to determine its importance in the regulation of proliferation and cell fate of cortical progenitors. We found strong nuclear localization in mature cells of astrocytic and neuronal lineages but weaker or absent nuclear localization in stem cells and oligodendroglial lineage cells. CIC loss-of-function studies showed increased proliferative and self-renewal capacity of neural stem/progenitor populations in vitro and in vivo. In addition, CIC loss biased cultured neural stem cells away from neuronal and astrocytic lineages and toward the oligodendrocyte lineage. Our data further suggest an overproduction of OPCs from cells in which CIC is lost. Taken together, our results indicate that CIC is an important regulator of fate decisions in neural development and suggest that its loss may contribute to oligodendroglioma formation by both dysregulating proliferation and by promoting an OPC-like identity.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".