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Record W4388221232 · doi:10.1016/j.stemcr.2023.10.005

AT7867 promotes pancreatic progenitor differentiation of human iPSCs

2023· article· en· W4388221232 on OpenAlexafffund
Nerea Cuesta‐Gomez, Kevin Verhoeff, Nidheesh Dadheech, Rena Pawlick, Braulio A. Marfil‐Garza, Haide Razavy, A. M. James Shapiro

Bibliographic record

VenueStem Cell Reports · 2023
Typearticle
Languageen
FieldMedicine
TopicPancreatic function and diabetes
Canadian institutionsUniversity of Alberta
FundersBreakthrough T1D CanadaAlberta Diabetes FoundationJuvenile Diabetes Research Foundation CanadaCanada Research ChairsStem Cell NetworkDiabetes CanadaDiabetes Research Institute Foundation
KeywordsPDX1BiologyProgenitor cellDownregulation and upregulationTransplantationInternal medicineStem cellAndrologyIn vivoEndocrinologyCellular differentiationDiabetes mellitusCell biologyIsletMedicineBiochemistryGene

Abstract

fetched live from OpenAlex

Generation of pure pancreatic progenitor (PP) cells is critical for clinical translation of stem cell-derived islets. Herein, we performed PP differentiation with and without AKT/P70 inhibitor AT7867 and characterized the resulting cells at protein and transcript level in vitro and in vivo upon transplantation into diabetic mice. AT7867 treatment increased the percentage of PDX1 + NKX6.1 + (−AT7867: 50.9% [IQR 48.9%–53.8%]; +AT7867: 90.8% [IQR 88.9%–93.7%]; p = 0.0021) and PDX1 + GP2 + PP cells (−AT7867: 39.22% [IQR 36.7%–44.1%]; +AT7867: 90.0% [IQR 88.2%–93.6%]; p = 0.0021). Transcriptionally, AT7867 treatment significantly upregulated PDX1 (p = 0.0001), NKX6 . 1 (p = 0.0005), and GP2 (p = 0.002) expression compared with controls, while off-target markers PODXL (p < 0.0001) and TBX2 (p < 0.0001) were significantly downregulated. Transplantation of AT7867-treated PPs resulted in faster hyperglycemia reversal in diabetic mice compared with controls (time and group: p < 0.0001). Overall, our data show that AT7867 enhances PP cell differentiation leading to accelerated diabetes reversal.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.201
Threshold uncertainty score0.400

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.023
GPT teacher head0.260
Teacher spread0.238 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations6
Published2023
Admission routes2
Has abstractyes

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