Global community effect: large-scale cooperation yields collective survival of differentiating embryonic stem cells [preprint]
Bibliographic record
Abstract
“Community effect” conventionally describes differentiation occurring only when enough cells help their local (micrometers-scale) neighbors differentiate. Although new community effects are being uncovered for myriad differentiations, macroscopic-scale community effects - fates of millions of cells all entangled across centimeters - remain elusive. We found that differentiating mouse Embryonic Stem (ES) cells that are scattered as individuals over many centimeters form one macroscopic entity via long-range communications. The macroscopic population avoids extinction only if its centimeter-scale density is above a threshold value. Single-cell-level measurements, transcriptomics, and mathematical modeling revealed that this “global community effect” occurs because differentiating ES-cell populations secrete, accumulate, and sense survival-promoting factors, including FGF4, that diffuse over many millimeters and activate Yap1-induced survival mechanisms. Only above-threshold-density populations accumulate above-threshold-concentrations of factors required to survive. We thus uncovered a previously overlooked, large-scale cooperation that underlies ES-cell differentiation. Tuning such large-scale cooperation may enable constructions of macroscopic, synthetic multicellular structures.
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How this classification was reachedexpand
Direct model labels (unvalidated)
Per-model category and study-design labels from the labeling rounds. They are machine output, unvalidated, and the disagreement between models ships as data. No study design here is MEDLINE-validated yet.
| Model arm | Categories | Study design | Confidence |
|---|---|---|---|
| gemma | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Bench or experimental | low |
| gpt | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Bench or experimental | high |
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 | 0.020 | 0.011 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.003 | 0.003 |
| Research integrity | 0.001 | 0.005 |
| 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, unvalidatedLabeled directly by 2 models reading the full record.
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".