Evidence map›Paper›PMID 41962865›Full record

ArticleThe Journal of biological chemistry2026

An artificial intelligence optimized hepatic differentiation unveils NR5A2 and AP-1 transcriptional regulation in hepatic maturation.

Zijun Huo, Jian Tu, Wei-Lei Yang, Mo-Fan Huang, Ruoyu Wang, Chih-Wei Chu, An Xu, Yao Yu, Tara N Tavakol, Mikal Kizilbash and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Zijun HuoDepartment of Endocrinology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China; Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Jian TuDepartment of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA; Department of Musculoskeletal Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China; Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China.
Wei-Lei YangAIxMed Inc. Santa Clara, California, USA.
Mo-Fan HuangDepartment of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, Texas, USA.
Ruoyu WangThe University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, Texas, USA; Department of Biochemistry and Molecular Biology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Chih-Wei ChuDepartment of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, Texas, USA.
An XuDepartment of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Yao YuDepartment of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Tara N TavakolDepartment of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Mikal KizilbashDepartment of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Megan E FisherDepartment of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, Texas, USA.
Yu-Wen HuangDepartment of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Dandan ZhuDepartment of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Trinh T T PhanDepartment of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Rachel ShoemakerDepartment of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, Texas, USA.
Ya-Wen ChenDepartment of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Institute for Airway Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Center for Epithelial and Airway Biology and Regeneration, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Yang ZhangCollege of Science, Harbin Institute of Technology (Shenzhen), Shenzhen, Guangdong, China.
Chad D HuffDepartment of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Shih-Yu ChenAIxMed Inc. Santa Clara, California, USA.
Tien-Jen LiuAIxMed Inc. Santa Clara, California, USA.
Haipeng XiaoDepartment of Endocrinology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China.
Dung-Fang LeeDepartment of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, Texas, USA; Center for Precision Health, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, Texas, USA. Electronic address: dung-fang.lee@uth.tmc.edu.
Ruiying ZhaoDepartment of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA. Electronic address: ruiying.zhao@uth.tmc.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The generation of hepatocyte-like cells (HLCs) from human pluripotent stem cells (hPSCs) holds great promise for drug discovery and cell-based therapy for liver disease. However, current differentiation protocols are complicated and unstable, and the underlying gene regulatory mechanisms of hepatic differentiation remain incompletely defined. Here, we developed a machine learning-based artificial intelligence (AI) tool using phase-contrast images of hepatic progenitor cells (HPCs), which are essential for generating HLCs. The AI tool significantly improves the success rate of hepatic differentiation without the need for immunostaining or lineage tracing. By optimizing the methodology, we achieved an impressive purity of 90 to 95% for HLCs derived from hPSCs, aided by the AI algorithm. Through further investigating transcriptomes and epigenomic changes, we discovered the pivotal roles of nuclear receptor subfamily 5 group A member 2 and activator protein-1 transcription factors in regulating the maturation of hepatocytes. Single-cell RNA sequencing demonstrated the upregulation of nuclear receptor subfamily 5 group A member 2 and activator protein-1 during hepatic differentiation. Importantly, mutation analysis and tumorigenesis assays confirmed the safety of this modified hepatic differentiation protocol. This work highlights the potential of combining AI algorithm and computational genomics to facilitate development of lineage differentiation and molecular mechanism study.

Indexed as

Artificial IntelligenceCell DifferentiationHepatocytesLiverReceptors, Cytoplasmic and NuclearTranscription Factor AP-1AnimalsHumansPluripotent Stem CellsTranscription, GeneticNR5A2 protein, humanReceptors, Cytoplasmic and NuclearTranscription Factor AP-1AP-1artificial intelligencehepatic differentiationmulti-omics studyNR5A2

Identifiers

PMID41962865
PMCPMC13185932

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.