| RRC ID |
59677
|
| 著者 |
Miyoshi M, Kakinuma S, Kamiya A, Tsunoda T, Tsuchiya J, Sato A, Kaneko S, Nitta S, Kawai-Kitahata F, Murakawa M, Itsui Y, Nakagawa M, Azuma S, Nakauchi H, Asahina Y, Watanabe M.
|
| タイトル |
LIM homeobox 2 promotes interaction between human iPS-derived hepatic progenitors and iPS-derived hepatic stellate-like cells.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Human induced pluripotent stem (iPS) cells can differentiate into hepatocyte lineages, although the phenotype of the differentiated cells is immature compared to adult hepatocytes. Improvement of cell-cell interactions between 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 hepatocytic maturation in iPS-HPCs, such as their capacity for albumin production. Next, we generated iPS cell lines overexpressing LIM homeobox 2 (LHX2), which suppresses myofibroblastic changes in HSCs in mice. Hepatocytic maturation 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 cell line (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 hepatocytic maturation of iPS-HPCs, and indicates that genetically modified iPS-HSCs will be of value for research into cell-cell interactions.
|
| 巻・号 |
9(1)
|
| ページ |
2072
|
| 公開日 |
2019-2-14
|
| DOI |
10.1038/s41598-018-37430-9
|
| PII |
10.1038/s41598-018-37430-9
|
| PMID |
30765795
|
| PMC |
PMC6376133
|
| MeSH |
Animals
Cell Communication / physiology
Cell Culture Techniques / methods
Cell Differentiation / physiology
Cell Line
Coculture Techniques / methods
Hepatic Stellate Cells / metabolism*
Hepatocytes / metabolism
Humans
Induced Pluripotent Stem Cells / metabolism*
LIM-Homeodomain Proteins / metabolism*
Liver / metabolism*
Mice
Transcription Factors / metabolism*
Up-Regulation / physiology
|
| IF |
4.011
|
| 引用数 |
3
|
| リソース情報 |
| ヒト・動物細胞 |
HiPS-RIKEN-2F(HPS0014) |
