167-LB: The Contribution of a- to ß-Cell Transdifferentiation in Gestational ß-Cell Expansion in Mouse
Bibliographic record
Abstract
Introduction: Pregnancy is characterized as a state of insulin resistance. To compensate for this, endocrine pancreatic β-cell mass (BCM) expansion occurs and is maximal at gestational day 18 (GD18) in mouse. There is evidence through lineage tracing of α-cells that they can replenish β-cells following β-cell loss/stress by α to β-cell transdifferentiation. In this study we sought to track the fate of α-cells during pregnancy to determine the contribution of α to β-cell transdifferentiation in gestational BCM expansion. Hypothesis: α to β-cell transdifferentiation will be higher during pregnancy compared to a non-pregnant animal. Materials and Methods: Glucagon-Cre/Rosa26-eYFP mice were time-mated and a non-pregnant group was age-matched to these animals. Pancreata were removed on GD9, 12, 18, and postpartum day 7 for fluorescence immunohistochemistry. Tissue sections were immunostained for insulin, YFP, glucagon, DAPI and analyzed by manual cell counting. All insulin-expressing cells were counted and separated into either islets (≥6 β-cells) or clusters (1-5 β-cells). Results: There were more transitional cells (Insulin+YFP+Glucagon+) in clusters during pregnancy compared to a non-pregnant animal (13.31±4.53%vs.9.14±2.01%). Furthermore, there were more differentiated β-cells with an α-cell origin (Insulin+YFP+Glucagon-) during pregnancy compared to a non-pregnant animal (16.73±5.28% vs.5.79±3.27%). Discussion and Conclusions: The data show more transitional cells during pregnancy, followed by an increase in β-cells differentiating from α-cells. Our previous experiments found that BCM expansion occurs in part due to neogenesis from β-cell progenitors located in clusters. Since there were more transitional cells localized to clusters, it is plausible that α to β cell transdifferentiation is enriched in clusters. This study provides mechanistic insights into the pathology of β-cell deficiency in pathological pregnancies such as gestational diabetes. Disclosure S. Szlapinski: None. J. Bennett: None. B. Strutt: None. D.J. Hill: None. Funding Ontario Graduate Scholarship; Lawson Foundation; St. Joseph’s Health Care Foundation
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.009 | 0.003 |
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".