Multiple sclerosis patient-derived CSF induces transcriptional changes in proliferating oligodendrocyte progenitors
Bibliographic record
Abstract
BACKGROUND: Cerebrospinal fluid (CSF) is in contact with brain parenchyma and ventricles, and its composition might influence the cellular physiology of oligodendrocyte progenitor cells (OPCs) thereby contributing to multiple sclerosis (MS) disease pathogenesis. OBJECTIVE: To identify the transcriptional changes that distinguish the transcriptional response induced in proliferating rat OPCs upon exposure to CSF from primary progressive multiple sclerosis (PPMS) or relapsing remitting multiple sclerosis (RRMS) patients and other neurological controls. METHODS: We performed gene microarray analysis of OPCs exposed to CSF from neurological controls, or definitive RRMS or PPMS disease course. Results were confirmed by quantitative reverse transcriptase polymerase chain reaction, immunocytochemistry and western blot of cultured cells, and validated in human brain specimens. RESULTS: We identified common and unique oligodendrocyte genes for each treatment group. Exposure to CSF from PPMS uniquely induced branching of cultured progenitors and related transcriptional changes, including upregulation (P<0.05) of the adhesion molecule GALECTIN-3/Lgals3, which was also detected at the protein level in brain specimens from PPMS patients. This pattern of gene expression was distinct from the transcriptional programme of oligodendrocyte differentiation during development. CONCLUSIONS: Despite evidence of morphological differentiation induced by exposure to CSF of PPMS patients, the overall transcriptional response elicited in cultured OPCs was consistent with the activation of an aberrant transcriptional programme.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| 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".