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Record W3165118996 · doi:10.1073/pnas.2104841118

AP-1 is a temporally regulated dual gatekeeper of reprogramming to pluripotency

2021· article· en· W3165118996 on OpenAlexfundno aff
Glenn J. Markov, Thach Mai, Surag Nair, Anna Shcherbina, Yu Xin Wang, David Burns, Anshul Kundaje, Helen M. Blau

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicPluripotent Stem Cells Research
Canadian institutionsnot available
FundersNational Institute of General Medical SciencesNational Human Genome Research InstituteNational Institute on AgingStanford Bio-XBaxter International FoundationNational Science FoundationGovernment of CanadaCanadian Institutes of Health ResearchLi Ka Shing Foundation
KeywordsReprogrammingEmbryonic stem cellCell biologySomatic cellBiologyStem cellRepressorInduced pluripotent stem cellGeneTranscription factorGeneticsMolecular biology

Abstract

fetched live from OpenAlex

Significance Reprogramming of somatic cells holds tremendous therapeutic promise. Here we show that a key barrier to this process is a DNA binding protein named activator protein 1 (AP-1). We find that AP-1 acts sequentially to first maintain the somatic state by turning genes on and then to block the initiation of the new cellular program by acting as a repressor of gene transcription. Crucially, we were able to uncover this feature of AP-1 by using the heterokaryon system of reprogramming, in which human fibroblasts are fused to an excess of mouse embryonic stem cells to favor the induction of the embryonic stem cell program in the fibroblast.

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)0.001
metaresearch head score (Gemma)0.001
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 score0.009
Threshold uncertainty score0.255

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
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 head0.034
GPT teacher head0.316
Teacher spread0.283 · 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

Citations50
Published2021
Admission routes1
Has abstractyes

Explore more

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