Vitamin C inactivates c-Jun N-terminal kinase to stabilize heart and neural crest derivatives expressed 1 in regulating placentation and pregnant maintenance
Bibliographic record
Abstract
Abstract Vitamin C (VC) is an essential nutrient for anti-oxidation, metabolic reaction, and stem cell differentiation. However, the precise role of VC in placentation and pregnant maintenance remains unknown. Here, we demonstrate that physiological concentration of VC stabilizes the Hand1, a bHLH transcription factor crucial for the development of trophoblast giant cell (TGC) lineage, to promote the differentiation of trophoblast stem cells into TGCs. The role of VC depends on the inactivation of JNK kinase, which directly phosphorylates Hand1 at Ser48 and thereby induces Hand1 proteasomal degradation, whereas loss-of-function mutation of Ser48 on Hand1 robustly decreases not only the basal but also VC-induced Hand1 stabilization. As a result, VC deficiency, lentiviral knockdown of JNK or overexpression of Hand1 mutants in trophectoderm significantly affects the differentiation of primary and secondary TGCs in E8.5 mouse placentas. VC deficiency causes a severe defect in the differentiation of diverse TGCs and the formation of vascular network of labyrinth in mature mouse placentas and thereby fails to maintain the pregnancy. Thus, these results uncover JNK inactivation and subsequent Hand1 stabilization as a hitherto uncharacterized mechanism controlling VC-mediated placentation and perhaps pregnant maintenance.
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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) | 0.002 | 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".