Epigenetic dosage identifies two major and functionally distinct β cell subtypes
Bibliographic record
Abstract
The mechanisms that specify and stabilize cell subtypes remain poorly understood. Here, we identify two major subtypes of pancreatic β cells based on histone mark heterogeneity (β HI and β LO ). β HI cells exhibit ∼4-fold higher levels of H3K27me3, distinct chromatin organization and compaction, and a specific transcriptional pattern. β HI and β LO cells also differ in size, morphology, cytosolic and nuclear ultrastructure, epigenomes, cell surface marker expression, and function, and can be FACS separated into CD24 + and CD24 − fractions. Functionally, β HI cells have increased mitochondrial mass, activity, and insulin secretion in vivo and ex vivo . Partial loss of function indicates that H3K27me3 dosage regulates β HI /β LO ratio in vivo , suggesting that control of β cell subtype identity and ratio is at least partially uncoupled . Both subtypes are conserved in humans, with β HI cells enriched in humans with type 2 diabetes. Thus, epigenetic dosage is a novel regulator of cell subtype specification and identifies two functionally distinct β cell subtypes.
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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) | 0.001 | 0.001 |
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; both teacher heads agree on what is shown here.
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".