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Record W3213709423 · doi:10.1038/s41467-021-26764-0

Generation of functional ciliated cholangiocytes from human pluripotent stem cells

2021· article· en· W3213709423 on OpenAlexafffund
Mina Ogawa, Jiaxin Jiang, Sunny Xia, Donghe Yang, Avrilynn Ding, Onofrio Laselva, Chang-Yi Cui, Yuichiro Higuchi, Hiroshi Suemizu, Craig Dorrell, Markus Grompe, Christine E. Bear, Shinichiro Ogawa

Bibliographic record

VenueNature Communications · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic and Kidney Cyst Diseases
Canadian institutionsUniversity of TorontoHospital for Sick ChildrenStem Cell NetworkUniversity Health Network
FundersHospital for Sick ChildrenUniversity of TorontoJapan Society for the Promotion of ScienceCanada First Research Excellence FundMinistry of Education, Culture, Sports, Science and TechnologyGovernment of CanadaSick Kids FoundationGenome CanadaOntario GenomicsOntario Genomics InstituteCystic Fibrosis Canada
KeywordsInduced pluripotent stem cellStem cellCell biologyBiologyHuman Induced Pluripotent Stem CellsComputational biologyEmbryonic stem cellGeneticsGene

Abstract

fetched live from OpenAlex

The derivation of mature functional cholangiocytes from human pluripotent stem cells (hPSCs) provides a model for studying the pathogenesis of cholangiopathies and for developing therapies to treat them. Current differentiation protocols are not efficient and give rise to cholangiocytes that are not fully mature, limiting their therapeutic applications. Here, we generate functional hPSC-derived cholangiocytes that display many characteristics of mature bile duct cells including high levels of cystic fibrosis transmembrane conductance regulator (CFTR) and the presence of primary cilia capable of sensing flow. With this level of maturation, these cholangiocytes are amenable for testing the efficacy of cystic fibrosis drugs and for studying the role of cilia in cholangiocyte development and function. Transplantation studies show that the mature cholangiocytes generate ductal structures in the liver of immunocompromised mice indicating that it may be possible to develop cell-based therapies to restore bile duct function in patients with biliary disease.

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 score0.003
Threshold uncertainty score0.010

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)0.0030.001

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 head0.040
GPT teacher head0.280
Teacher spread0.240 · 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

Citations45
Published2021
Admission routes2
Has abstractyes

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Same venueNature CommunicationsSame topicGenetic and Kidney Cyst DiseasesFrench-language works237,207