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Record W4403276034 · doi:10.1038/s41467-024-53068-w

Tankyrase inhibition promotes endocrine commitment of hPSC-derived pancreatic progenitors

2024· article· en· W4403276034 on OpenAlexafffund
Frankie Poon, Rangarajan Sambathkumar, Roman Korytnikov, Yasaman Aghazadeh, Amanda Oakie, Paraish S. Misra, Farida Sarangi, M. Cristina Nostro

Bibliographic record

VenueNature Communications · 2024
Typearticle
Languageen
FieldMedicine
TopicPancreatic function and diabetes
Canadian institutionsMontreal Clinical Research InstituteMcMaster UniversityUniversity of TorontoUniversity Health Network
FundersCIHR Skin Research Training CentreBanting and Best Diabetes Centre, University of TorontoEli Lilly CanadaGovernment of CanadaNatural Sciences and Engineering Research Council of CanadaJuvenile Diabetes Research Foundation United States of AmericaToronto General and Western Hospital FoundationJuvenile Diabetes Research Foundation CanadaLeona M. and Harry B. Helmsley Charitable TrustToronto General Hospital Research Institute, University Health NetworkCanadian Society of TransplantationEli Lilly and Company
KeywordsEndocrine systemProgenitor cellProgenitorCell biologyEnteroendocrine cellBiologyEndocrinologyStem cellHormone

Abstract

fetched live from OpenAlex

Human pluripotent stem cells (hPSCs) have the potential to differentiate into various cell types, including pancreatic insulin-producing β cells, which are crucial for developing therapies for diabetes. However, current methods for directing hPSC differentiation towards pancreatic β-like cells are often inefficient and produce cells that do not fully resemble the native counterparts. Here, we report that highly selective tankyrase inhibitors, such as WIKI4, significantly enhances pancreatic differentiation from hPSCs. Our results show that WIKI4 promotes the formation of pancreatic progenitors that give rise to islet-like cells with improved β-like cell frequencies and glucose responsiveness compared to our standard cultures. These findings not only advance our understanding of pancreatic development, but also provide a promising new tool for generating pancreatic cells for research and potential therapeutic applications. “Here the authors demonstrate that ß cell differentiation from human pluripotent stem cells can be improved by replacing nicotinamide with tankyrase inhibitors. This results in pancreatic progenitors that form islet-like cells with increased ß cell frequencies and glucose responsiveness.”

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.001
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.001

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.

Opus teacher head0.023
GPT teacher head0.312
Teacher spread0.290 · 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 source (direct Gemma or distilled Codex), 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
Published2024
Admission routes2
Has abstractyes

Explore more

Same venueNature Communications→Same topicPancreatic function and diabetes→French-language works237,207→