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Record W3112834042 · doi:10.1016/j.celrep.2020.108455

Large-scale Generation of Functional and Transplantable Hepatocytes and Cholangiocytes from Human Endoderm Stem Cells

2020· article· en· W3112834042 on OpenAlexaff
Sisi Feng, Jiaying Wu, Wei‐Lin Qiu, Yang Li, Xiaogang Deng, Ying Zhou, Yabin Chen, Li Xiao, Lei Yu, Hongsheng Li, Ziran Xu, Yini Xiao, Xiongzhao Ren, Ludi Zhang, Chenhua Wang, Zhen Sun, Jinglin Wang, Xiaoyan Ding, Yue‐Lei Chen, Paul Gadue, Guoyu Pan, Mina Ogawa, Shinichiro Ogawa, Jie Na, Peilin Zhang, Lijian Hui, Hao Yin, Luonan Chen, Cheng‐Ran Xu, Xin Cheng

Bibliographic record

VenueCell Reports · 2020
Typearticle
Languageen
FieldMedicine
TopicLiver physiology and pathology
Canadian institutionsUniversity Health Network
FundersNational Key Research and Development Program of ChinaScience and Technology Commission of Shanghai MunicipalityNational Natural Science Foundation of China
KeywordsCell biologyEndodermStem cellBiologyIn vitroIn vivoTranscriptomeHepatocyteMesenchymal stem cellHepatic stellate cellEmbryonic stem cellEndocrinologyBiochemistryGeneBiotechnologyGene expression

Abstract

fetched live from OpenAlex

The ever-increasing therapeutic and pharmaceutical demand for liver cells calls for systems that enable mass production of hepatic cells. Here we describe a large-scale suspension system that uses human endoderm stem cells (hEnSCs) as precursors to generate functional and transplantable hepatocytes (E-heps) or cholangiocytes (E-chos). hEnSC-derived hepatic populations are characterized by single-cell transcriptomic analyses and compared with hESC-derived counterparts, in-vitro-maintained or -expanded primary hepatocytes and adult cells, which reveals that hepatic differentiation of hEnSCs recapitulates in vivo development and that the heterogeneities of the resultant populations can be manipulated by regulating the EGF and MAPK signaling pathways. Functional assessments demonstrate that E-heps and E-chos possess properties comparable with adult counterparts and that, when transplanted intraperitoneally, encapsulated E-heps were able to rescue rats with acute liver failure. Our study lays the foundation for cell-based therapeutic agents and in vitro applications for liver diseases.

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 score0.044
Threshold uncertainty score0.283

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 head0.036
GPT teacher head0.228
Teacher spread0.191 · 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

Citations42
Published2020
Admission routes1
Has abstractyes

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