Induction of cellular totipotency by NACC1-driven feed-forward regulation
Bibliographic record
Abstract
SUMMARY Mammalian embryo development begins with totipotent cells. Despite its significance, gene regulatory mechanisms controlling the totipotent cell stage are poorly understood. Based on single-cell proteomics and transcriptomics, we identified nucleus accumbens-associated 1 (NACC1) as a critical regulator of totipotent-like cell state in mouse embryonic stem cells. Using a combination of genomics approaches, we found that NACC1 directly binds to gene-regulatory regions and favours chromatin accessibility to induce the expression of totipotency and zygotic genome activation genes, as well as retrotransposons associated with totipotency. In parallel, NACC1-regulated retrotransposons further modulate the expression of proximal totipotency genes, forming a coherent feed-forward mechanism that regulates totipotent-like cells. Furthermore, NACC1 is crucial for the progression of embryogenesis beyond the totipotency stage. Thus, we uncover a genome-level NACC1-driven feed-forward gene regulatory mechanism that governs totipotent-like cells and has a crucial role during embryonic development.
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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) | 0.001 | 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".