Vegfr3 activation of Pkd2l1+ CSF-cNs triggers the neural stem cell response in spinal cord injury
Bibliographic record
Abstract
Activating adult neural stem cells (NSCs) located within the spinal cord niche is considered a promising therapeutic approach for treating spinal cord injury (SCI). Cerebrospinal fluid (CSF)-contacting neurons expressing Pkd2l1 exhibit phenotypic and molecular traits similar to those of adult NSCs. However, the mechanism responsible for regulating the activation of Pkd2l1 + CSF-cNs still needs to be discovered. This research demonstrated that Pkd2l1 + CSF-cNs have a high concentration of vascular endothelial growth factor receptor 3 (Vegfr3) and that SCI results in elevated Vegfr3 levels. The overexpression of Vegfr3 in Pkd2l1 + CSF-cNs induced potential NSC activation. Blocking Vegfr3 led to a significant reduction in the percentage of active Pkd2l1 + CSF-cNs, suggesting that Vegfr3 is involved in controlling the shift from dormancy to activation in these cells. In vivo, the downregulation of Vegfr3 by SAR131475 inhibited Pkd2l1 + CSF-cN proliferation and maintained self-renewal. Injection of vascular endothelial growth factor C (Vegf-C) into the lateral ventricle of adult mice confirmed the involvement of Vegfr3 in activating Pkd2l1 + CSF-cNs. Vegf-C administration significantly increased the number of activated Pkd2l1 + CSF-cNs. Mechanistically, Vegfr3 primed quiescent Pkd2l1 + CSF-cNs for cell cycle reentry by enabling the activation of PI3K/Akt signaling. The activation of Vegfr3 may enhance SCI outcomes by promoting neuronal survival and facilitating the recovery of motor function in mice. Together, our findings highlight that Vegfr3 is a crucial functional regulator of Pkd2l1 + CSF-cNs, governing the transition from NSC quiescence to activation. • Vegfr3 overexpression in Pkd2l1 + CSF-cNs activates neural stem cell potential, promoting neuro-regeneration. • Vegfr3 inhibition by SAR131475 reduces CSF-cN activation and proliferation, highlighting its physiological role. • Vegf-C enhances Vegfr3-mediated Pkd2l1 + CSF-cNs activation, aiding SCI recovery via neuronal survival. • Vegfr3 drives quiescent Pkd2l1 + CSF-cNs into cell cycle via PI3K/Akt, revealing neural stem cell activation mechanisms.
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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 | 0.000 |
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".