LIM homeobox 2 promotes interaction between human iPS-derived hepatic progenitors and iPS-derived hepatic stellate-like cells
2019
Human induced pluripotent stem (iPS) cells can differentiate into
hepatocytelineages, although the phenotype of the differentiated cells is immature compared to adult
hepatocytes. Improvement of
cell-cell interactionsbetween epithelium and mesenchyme is a potential approach to address this phenotype issue. In this study, we developed a model system for improving interactions between human iPS-derived hepatic progenitor cells (iPS-HPCs) and human iPS-derived
hepatic stellate cell-like cells (iPS-HSCs). The phenotype of iPS-HSCs, including gene and protein expression profiles and vitamin A storage, resembled that of
hepatic stellate cells. Direct co-culture of iPS-HSCs with iPS-HPCs significantly improved
hepatocyticmaturation in iPS-HPCs, such as their capacity for albumin production. Next, we generated iPS cell lines overexpressing LIM
homeobox2 (LHX2), which suppresses myofibroblastic changes in HSCs in mice.
Hepatocyticmaturation in iPS-HPCs was significantly increased in direct co-culture with iPS-HSCs overexpressing LHX2, but not in co-culture with a human
hepatic stellate cellline (LX-2) overexpressing LHX2. LHX2 regulated the expression of extracellular matrices, such as laminin and collagen, in iPS-HSCs. In conclusion, this study provides an evidence that LHX2 upregulation in iPS-HSCs promotes
hepatocyticmaturation of iPS-HPCs, and indicates that genetically modified iPS-HSCs will be of value for research into
cell-cell interactions.
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