ArticleScientific reports2016
Connexin 32-mediated cell-cell communication is essential for hepatic differentiation from human embryonic stem cells.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 43 citations in OpenAlex.
- An artificial intelligence optimized hepatic differentiation unveils NR5A2 and AP-1 transcriptional regulation in hepatic maturation.The Journal of biological chemistry · 2026Article
- Deceiving the gatekeepers: virus modulation of gap junctions.Microbiology and molecular biology reviews : MMBR · 2025Review
- Single-cell multi-omics deciphers hepatocyte dedifferentiation and illuminates maintenance strategies.Cell proliferation · 2025Article
- Role of connexin 32 in the directional differentiation of induced pluripotent stem cells into hepatocytes.International journal of medical sciences · 2024Article
- Platform-agnostic CellNet enables cross-study analysis of cell fate engineering protocols.Stem cell reports · 2023Article
- The Potential Role of Connexins in the Pathogenesis of Atherosclerosis.International journal of molecular sciences · 2023Review
- The Multifaceted Role of Connexins in Tumor Microenvironment Initiation and Maintenance.Biology · 2023Review
- Harnessing conserved signaling and metabolic pathways to enhance the maturation of functional engineered tissues.NPJ Regenerative medicine · 2022Review
- Article
- Exploiting three-dimensional human hepatic constructs to investigate the impact of rs174537 on fatty acid metabolism.PloS one · 2022Article
- Connexin 43 Gene Ablation Does Not Alter Human Pluripotent Stem Cell Germ Lineage Specification.Biomolecules · 2021Article
- Connexins in the development and physiology of stem cells.Tissue barriers · 2021Review
- Global Gene Expression Profiling Reveals Isorhamnetin Induces Hepatic-Lineage Specific Differentiation in Human Amniotic Epithelial Cells.Frontiers in cell and developmental biology · 2020Article
- Human ESC-derived expandable hepatic organoids enable therapeutic liver repopulation and pathophysiological modeling of alcoholic liver injury.Cell research · 2019Article
- Low-density lipoprotein receptor-deficient hepatocytes differentiated from induced pluripotent stem cells allow familial hypercholesterolemia modeling, CRISPR/Cas-mediated genetic correction, and productive hepatitis C virus infection.Stem cell research & therapy · 2019Article
- Binding of α-synuclein oligomers to Cx32 facilitates protein uptake and transfer in neurons and oligodendrocytes.Acta neuropathologica · 2019Article
- A Comparative Assessment of Human and Chimpanzee iPSC-derived Cardiomyocytes with Primary Heart Tissues.Scientific reports · 2018Article
- Connexins: Synthesis, Post-Translational Modifications, and Trafficking in Health and Disease.International journal of molecular sciences · 2018Review
- Generation of human embryonic stem cell line with heterozygous RB1 deletion by CRIPSR/Cas9 nickase.Stem cell research · 2018Article
- Connexin 32 and connexin 43 are involved in lineage restriction of hepatic progenitor cells to hepatocytes.Stem cell research & therapy · 2017Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Gap junction-mediated cell-cell interactions are highly conserved and play essential roles in cell survival, proliferation, differentiation and patterning. We report that Connexin 32 (Cx32)-mediated gap junctional intercellular communication (GJIC) is necessary for human embryonic stem cell-derived hepatocytes (hESC-Heps) during step-wise hepatic lineage restriction and maturation. Vitamin K2, previously shown to promote Cx32 expression in mature hepatocytes, up-regulated Cx32 expression and GJIC activation during hepatic differentiation and maturation, resulting in significant increases of hepatic markers expression and hepatocyte functions. In contrast, negative Cx32 regulator 2-aminoethoxydiphenyl borate blocked hESC-to-hepatocyte maturation and muted hepatocyte functions through disruption of GJIC activities. Dynamic gap junction organization and internalization are phosphorylation-dependent and the p38 mitogen-activated protein kinases pathway (MAPK) can negatively regulate Cxs through phosphorylation-dependent degradation of Cxs. We found that p38 MAPK inhibitor SB203580 improved maturation of hESC-Heps correlating with up-regulation of Cx32; by contrast, the p38 MAPK activator, anisomycin, blocked hESC-Heps maturation correlating with down-regulation of Cx32. These results suggested that Cx32 is essential for cell-cell interactions that facilitate driving hESCs through hepatic-lineage maturation. Regulators of both Cx32 and other members of its pathways maybe used as a promising approach on regulating hepatic lineage restriction of pluripotent stem cells and optimizing their functional maturation.
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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.