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Human ESC/iPSC-Derived Hepatocyte-like Cells Achieve Zone-Specific Hepatic Properties by Modulation of WNT Signaling.
- Source :
-
Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2017 Jun 07; Vol. 25 (6), pp. 1420-1433. Date of Electronic Publication: 2017 Apr 24. - Publication Year :
- 2017
-
Abstract
- The function of hepatocytes largely depends on their position in the liver lobule. Although the method of differentiating hepatocytes from human pluripotent stem cells has been largely improved over the past decade, there remains no technique for generating hepatocyte-like cells (HLCs) with zone-specific hepatic properties. In this study, we searched for the factors that promote acquisition of zone-specific properties of HLCs. Here, we identified that WNT7B and WNT8B secreted from hepatocytes and cholangiocytes play important roles in achieving perivenous zone-specific characteristics, such as the enhancement of glutamine secretion, citric acid cycle, cytochrome P450 (CYP) 1A2 metabolism, and CYP1A2 induction capacities. We also found that WNT inhibitory factor (WIF-1) secreted from cholangiocytes was necessary for achieving periportal zone-specific characteristics, such as the enhancement of urea secretion and gluconeogenesis capacities. Therefore, WNT signal modulators secreted from hepatocytes or cholangiocytes conferred zone-specific hepatic properties onto HLCs.<br /> (Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adaptor Proteins, Signal Transducing genetics
Animals
Biomarkers
Cell Line
Cells, Cultured
Culture Media, Conditioned pharmacology
Energy Metabolism
Fibroblasts metabolism
Gene Expression Profiling
Gene Expression Regulation, Developmental
Gene Expression Regulation, Enzymologic
Gene Knockdown Techniques
Hepatocytes cytology
Humans
Mice
Pharmacogenetics
RNA, Small Interfering genetics
Repressor Proteins genetics
Wnt Proteins genetics
Wnt Proteins metabolism
Cell Differentiation genetics
Embryonic Stem Cells cytology
Embryonic Stem Cells metabolism
Hepatocytes metabolism
Induced Pluripotent Stem Cells cytology
Induced Pluripotent Stem Cells metabolism
Wnt Signaling Pathway drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1525-0024
- Volume :
- 25
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Molecular therapy : the journal of the American Society of Gene Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 28462819
- Full Text :
- https://doi.org/10.1016/j.ymthe.2017.04.006