Functional analysis of gene regulation in oligodendrocyte progenitor cells
Bibliographic record
Abstract
Myelin is elaborated in the Central Nervous System (CNS) by oligodendrocytes and is essential for rapid action potential conduction. During embryogenesis and early postnatal stages of CNS development, oligodendrocyte progenitor cells (OPCs) proliferate and migrate in response to platelet derived growth factor-A (PDGF-A), the ligand for PDGFRa. This study describes the identification of regulatory elements and potential corresponding transcription factors controlling PDGFRa expression in OPCs, which will contribute to a better understanding of oligodendroglial lineage specification including OPC proliferation, migration and final maturation. Based on previous studies, the enhancer(s) driving expression in oligodendrocytes was only known to be located somewhere within a 380kb yeast artificial chromosome (YAC). To refine the search, a transgenic mouse line containing a bacterial artificial chromosome (BAC), containing a lacZ reporter gene, was generated. The lacZ reporter gene was inserted into the BAC, using a recombineering strategy. This line contains an 87kb BAC (CTD-2243G22) that starts –16kb upstream of the transcription start site, and ends +2kb downstream of the 3'UTR. It demonstrates robust lacZ expression in brain regions where OPCs originate. Based on interspecies sequence comparison and the presence of relevant transcription factor binding sites, such as for Sox and oligs, four candidate non-protein coding modules were identified within the 87kb defined by the BAC. These modules are being evaluated for in vivo function in the context of lacZ reporter genes docked at the hypoxanthine phosphoribosyl transferase (HPRT) locus. One of these constructs, which contains 600bp of intron 21 of the PDGFRa gene, shows a similar pattern of expression to the BAC, suggesting that the sequence containing the OPC enhancer may have been captured out of a 380kb region. Deletions have been made in this 600bp, to discover which eleme
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".