ArticleStem cells (Dayton, Ohio)2013
Insulin and IGFs enhance hepatocyte differentiation from human embryonic stem cells via the PI3K/AKT pathway.
Article in Stem cells (Dayton, Ohio), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 78 citations in OpenAlex.
- Leveraging IGF signaling to improve the spatial organization and regenerative potential of iPSC-derived vascularized liver organoids.Science advances · 2026Article
- Endometriosis: Epidemiology, Risk Factors, Molecular Mechanisms, Diagnosis, and Management.MedComm · 2026Review
- CDX2 Promotes Hepatic Specification of hiPSC-derived Endoderm Through the PI3K-Akt-GSK3β Pathway for Improved Therapeutic Efficacy.Stem cell reviews and reports · 2026Article
- The role of IGF/IGF-1R signaling in the regulation of cancer stem cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Review
- Small hepatitis B virus surface antigen (SHBs) induces dyslipidemia by suppressing apolipoprotein-AII expression through ER stress-mediated modulation of HNF4α and C/EBPγ.Journal of virology · 2024Article
- Multi-organ developmental toxicity and its characteristics in fetal mice induced by dexamethasone at different doses, stages, and courses during pregnancy.Archives of toxicology · 2024Article
- Schisandrin B promotes hepatic differentiation from human umbilical cord mesenchymal stem cells.iScience · 2024Article
- In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4Vaccines · 2023Article
- Imprinted Dlk1-Gtl2 cluster miRNAs are potential epigenetic regulators of lamb fur quality.BMC genomics · 2023Article
- Article
- Developmental toxicity and programming alterations of multiple organs in offspring induced by medication during pregnancy.Acta pharmaceutica Sinica. B · 2023Review
- Retinoids rescue ceruloplasmin secretion and alleviate oxidative stress in Wilson's disease-specific hepatocytes.Human molecular genetics · 2022Article
- Mini Review: Molecular Interpretation of the IGF/IGF-1R Axis in Cancer Treatment and Stem Cells-Based Therapy in Regenerative Medicine.International journal of molecular sciences · 2022Review
- Efficient Generation of Functional Hepatocytes from Human Induced Pluripotent Stem Cells for Disease Modeling and Disease Gene Discovery.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Elevated levels of expression of cytochrome P450 3A4 in a human liver epithelial cell line in differentiation-inducing conditions.Human cell · 2021Article
- O-1602 Promotes Hepatic Steatosis through GPR55 and PI3 Kinase/Akt/SREBP-1c Signaling in Mice.International journal of molecular sciences · 2021Article
- Current status of hepatocyte-like cell therapy from stem cells.Surgery today · 2021Review
- [Research progress of hepatocyte transplantation treatment for alpha-1 antitrypsin deficiency].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2020Article
- Article
- Urine-derived stem cells accelerate the recovery of injured mouse hepatic tissue.American journal of translational research · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Human embryonic stem cells (hESCs) can be progressively differentiated into definitive endoderm (DE), hepatic progenitors, and hepatocytes, and thus provide an excellent model system for the mechanistic study of hepatocyte differentiation, which is currently poorly understood. Here, we found that insulin enhanced hepatocyte differentiation from hESC-derived DE. Insulin activated the PI3K/AKT pathway, but not the mitogen-activated protein kinase pathway in the DE cells, and inhibition of the PI3K/AKT pathways by inhibitors markedly inhibited hepatocyte differentiation. In addition, insulin-like growth factor 1 (IGF1) and IGF2 also activated the PI3K/AKT pathway in DE cells and their expression was robustly upregulated during hepatocyte differentiation from DE. Furthermore, inhibition of IGF receptor 1 (IGF1R) by a small molecule inhibitor PPP or knockdown of the IGF1R by shRNA attenuated hepatocyte differentiation. Moreover, simultaneous knockdown of the IGF1R and the insulin receptor with shRNAs markedly reduced the activation of AKT and substantially impaired hepatocyte differentiation. The PI3K pathway specifically enhanced the expression of HNF1 and HNF4 to regulate hepatocyte differentiation from DE. Although inhibition of the PI3K pathway was previously shown to be required for the induction of DE from hESCs, our study revealed a positive role of the PI3K pathway in hepatocyte differentiation after the DE stage, and has advanced our understanding of hepatocyte cell fate determination.
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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.