ArticleCells2022
Hepatic Polarized Differentiation Promoted the Maturity and Liver Function of Human Embryonic Stem Cell-Derived Hepatocytes via Activating Hippo and AMPK Signaling Pathways.
Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- Modeling pathogenesis and progression of metabolic dysfunction-associated steatotic liver disease and therapeutic drug screening using hESC-derived mature polarized hepatocyte organoids.Stem cell research & therapy · 2025Article
- Large-Scale Production of Expandable Hepatoblast Organoids and Polarised Hepatocyte Organoids From hESCs Under 3D Static and Dynamic Suspension Conditions.Cell proliferation · 2025Article
- Distinct Roles of Matrigel Enabled the Production of Expandable Hepatoblast and Polarized Hepatocyte Organoids from Human Embryonic Stem Cells under 3-Dimensional Suspension Conditions.Biomaterials research · 2025Article
- Study on the Extrapolability of Current Tumorgenicity Test With Mice by Comparing the Syngeneic or Allogeneic Mouse Transplantation Model.Stem cells translational medicine · 2024Article
- Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocytes exhibit a multi-polarized state under the in vivo physiological environment, however, human embryonic stem cell-derived hepatocytes (hEHs) rarely exhibit polarity features in a two-dimensional (2D) condition. Thus, we hypothesized whether the polarized differentiation might enhance the maturity and liver function of hEHs. In this study, we obtained the polarized hEHs (phEHs) by using 2D differentiation in conjunct with employing transwell-based polarized culture. Our results showed that phEHs directionally secreted albumin, urea and bile acids, and afterward, the apical membrane and blood-bile barrier (BBIB) were identified to form in phEHs. Moreover, phEHs exhibited a higher maturity and capacitity of cellular secretory and drug metabolism than those of non-phEHs. Through transcriptome analysis, it was found that the polarized differentiation induced obvious changes in gene expression profiles of cellular adhesion and membrane transport in hEHs. Our further investigation revealed that the activation of Hippo and AMPK signaling pathways made contributions to the regulation of function and cellular polarity in phEHs, further verifying that the liver function of hEHs was closely related with their polarization state. These results not only demonstrated that the polarized differentiation enhanced the maturity and liver function of hEHs, but also identified the molecular targets that regulated the polarization state of hEHs.
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Registered trials
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.