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LIM homeobox 2 promotes interaction between human iPS-derived hepatic progenitors and iPS-derived hepatic stellate-like cells
- Source :
- Scientific Reports, Vol 9, Iss 1, Pp 1-13 (2019), Scientific Reports
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
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.
- Subjects :
- 0301 basic medicine
Mesenchyme
Cellular differentiation
Induced Pluripotent Stem Cells
LIM-Homeodomain Proteins
Cell Culture Techniques
lcsh:Medicine
Cell Communication
Biology
Article
Cell Line
Mice
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Hepatic Stellate Cells
medicine
Animals
Humans
Progenitor cell
lcsh:Science
Induced pluripotent stem cell
Multidisciplinary
lcsh:R
Cell Differentiation
Coculture Techniques
Up-Regulation
Cell biology
030104 developmental biology
medicine.anatomical_structure
Liver
Cell culture
Hepatocyte
embryonic structures
Hepatocytes
Hepatic stellate cell
lcsh:Q
030217 neurology & neurosurgery
Transcription Factors
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....31fb02530ee2ee788fe9a5edc6b66cd9
- Full Text :
- https://doi.org/10.1038/s41598-018-37430-9