Nac1 Coordinates a Sub-network of Pluripotency Factors to Regulate Embryonic Stem Cell Differentiation
Bibliographic record
Abstract
Pluripotent cells give rise to distinct cell types during development and are regulated by often self-reinforcing molecular networks. How such networks allow cells to differentiate is less well understood. Here, we use integrative methods to show that external signals induce reorganization of the mouse embryonic stem cell pluripotency network and that a sub-network of four factors, Nac1, Oct4, Tcf3, and Sox2, regulates their differentiation into the alternative mesendodermal and neuroectodermal fates. In the mesendodermal fate, Nac1 and Oct4 were constrained within quantitative windows, whereas Sox2 and Tcf3 were repressed. In contrast, in the neuroectodermal fate, Sox2 and Tcf3 were constrained while Nac1 and Oct4 were repressed. In addition, we show that Nac1 coordinates differentiation by activating Oct4 and inhibiting both Sox2 and Tcf3. Reorganization of progenitor cell networks around shared factors might be a common differentiation strategy and our integrative approach provides a general methodology for delineating such networks.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 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) | 0.000 | 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".