Peer-Reviewed Publication
J Biol Chem2026;302(6):111435.June 1, 2026Journal Article
An artificial intelligence optimized hepatic differentiation unveils NR5A2 and AP-1 transcriptional regulation in hepatic maturation.
Zijun Huo1, Jian Tu2, Wei-Lei Yang3, Mo-Fan Huang4, Ruoyu Wang5, Chih-Wei Chu4, An Xu6, Yao Yu7, Tara N Tavakol8, Mikal Kizilbash8, Megan E Fisher4, Yu-Wen Huang6, Dandan Zhu6, Trinh T T Phan6, Rachel Shoemaker4, Ya-Wen Chen9, Yang Zhang10, Chad D Huff11, Shih-Yu Chen3, Tien-Jen Liu3, Haipeng Xiao12, Dung-Fang Lee13, Ruiying Zhao14
1Department 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.
2Department 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.
3AIxMed Inc. Santa Clara, California, USA.
4Department 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.
5The 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.
6Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
7Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
8Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
9Department 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.
10College of Science, Harbin Institute of Technology (Shenzhen), Shenzhen, Guangdong, China.
11Department 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.
12Department of Endocrinology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China.
13Department 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.
14Department 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.
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…
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