SUN-146 Do highly-connected beta cell hubs overlap with epigenetically-defined BetaHi cells?
Bibliographic record
Abstract
Abstract G. Ostinelli: None. P. Carapeto: None. Z. Kabbash: None. E. Dror: None. J. Pospsisilik: None. G.A. Rutter: None. The adult beta cell is highly specialized and long-lived, and deploys epigenetic control to maintain its stability over time. These mechanisms may also be important to achieve beta cell heterogeneity, which is important to ensure normal glucose-stimulated insulin release. Recent work has described “Beta Hi” and “Beta Lo” populations defined by increased or decreased trimethylation, respectively, on lysine 27 of histone 3 (H3K27 me3). “Beta Hi” cells are also characterized by higher nuclear compaction, insulin content and release, as well as an increased number of mitochondria compared to “Beta Lo” cells. Interestingly, the two subgroups differ in terms of the expression of the cell surface marker CD24, with “Beta Hi” cells enriched for the latter. The extent to which these sub-groups may align with beta cell function, and their ability to coordinate calcium waves dictating insulin secretion, is unclear. In particular, whether subpopulations from which calcium oscillations emanate (“leaders”) or are coordinated (“hubs”) present an enrichment for CD24 is still unknown. Our objective here was to determine whether, and to what extent, CD24+ cells (“Beta Hi”), overlap with highly-connected “hub” cells. In order to do this, islets were isolated from Ins-Cre:GCaMP6LoxP mice and then transfected with an adenovirus expressing Photo Activatable (PA)-mCherry. Calcium waves were recorded by confocal imaging (Zeiss Airyscan) and analysed using ImageJ and MATLAB. Hubs were identified and labelled by photoexcitation of PA-mCherry. Islets were then fixed, and immunostaining performed to identify CD24+ cells. Our findings suggest that hubs cells display an enrichment of CD24 compared to followers, suggesting that hubs may belong to the “Beta Hi” subpopulation. Future studies will be needed to assess to which sub-population “leader” cells belong, and whether these assignations are altered in models of type 2 diabetes. Sunday, June 2, 2024
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 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; 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".