Overexpression of PAX4 reduces glucagon expression in differentiating hESCs
Bibliographic record
Abstract
Human embryonic stem cells (hESCs) are pluripotent and capable of generating new β-cells, but current in vitro differentiation protocols generally fail to produce mature, glucose-responsive, unihormonal β-cells. Instead, these methods tend to produce immature polyhormonal endocrine cells which mature in vivo into glucagon-positive α-cells. PAX4 is an established transcription factor in β-cell development and function, and is capable of converting glucagon-positive cells to insulin-positive cells in mice. Work in human and mouse ESCs has shown that constitutive PAX4 expression promotes the development of insulin-positive cells, but whether acute PAX4 expression is sufficient to guide specific endocrine cell fates has not been addressed in hESCs. In this study, we applied recombinant adenovirus to ectopically express human PAX4 in hESC-derived pancreatic progenitors, with the aim of influencing the endocrine developmental cascade away from polyhormonal cells toward unihormonal insulin-positive cells. Gene delivery to pancreatic progenitors was efficient and dose-dependent. By the end of in vitro differentiation, PAX4 reduced ARX expression, but only the high dose tested significantly reduced glucagon release. Single cell analysis revealed that while PAX4 did not alter the proportion of endocrine cells, it did reduce the number of glucagon-positive cells and increased the number of unihormonal insulin-positive cells. These data suggest that acute PAX4 overexpression can reduce expression of ARX and glucagon resulting in improved numbers of unihormonal insulin-positive cells.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".