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| Status |
Public on Feb 12, 2017 |
| Title |
Connexin 32-mediated cell-cell communication is essential for hepatic differentiation from human embryonic stem cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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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| Overall design |
Human embryonic stem cells (hESCs) were differentiated to hepatocytes with SB203580(SB) and Vitamin K2 (VK2). Primary human hepatocytes (PHHs)were isolated from adult liver tissues and fetal human hepatocytes (FHHs) were isolated from aborted fetal liver. We used RNA sequencing to detail the global gene expression profile of ESCs-derived hepatocytes with the treatment of SB or VK2, untreated control (Ctrl), PHHs and FHHs to delineate the difference of these cells.
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| Contributor(s) |
Qin J, Zhu W, Liu Z, Wang Y, Pei X |
| Citation(s) |
27874032 |
| Submission date |
Dec 17, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Jinhua Qin |
| E-mail(s) |
qinjinhuarhea@126.com
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| Organization name |
Beijing Institute of Transfusion
|
| Street address |
Taiping Road
|
| City |
Beijing |
| ZIP/Postal code |
100850 |
| Country |
China |
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| Platforms (2) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA306224 |
| SRA |
SRP067492 |
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