論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HiPS-RIKEN-2F(HPS0014) |