| RRC ID |
36954
|
| Author |
Tsuruya K, Chikada H, Ida K, Anzai K, Kagawa T, Inagaki Y, Mine T, Kamiya A.
|
| Title |
A Paracrine Mechanism Accelerating Expansion of Human Induced Pluripotent Stem Cell-Derived Hepatic Progenitor-Like Cells.
|
| Journal |
Stem Cells Dev
|
| Abstract |
Hepatic stem/progenitor cells in liver development have a high proliferative potential and the ability to differentiate into both hepatocytes and cholangiocytes. In this study, we focused on the cell surface molecules of human induced pluripotent stem (iPS) cell-derived hepatic progenitor-like cells (HPCs) and analyzed how these molecules modulate expansion of these cells. Human iPS cells were differentiated into immature hepatic lineage cells by cytokines. In addition to hepatic progenitor markers (CD13 and CD133), the cells were coimmunostained for various cell surface markers (116 types). The cells were analyzed by flow cytometry and in vitro colony formation culture with feeder cells. Twenty types of cell surface molecules were highly expressed in CD13(+)CD133(+) cells derived from human iPS cells. Of these molecules, CD221 (insulin-like growth factor receptor), which was expressed in CD13(+)CD133(+) cells, was quickly downregulated after in vitro expansion. The proliferative ability was suppressed by a neutralizing antibody and specific inhibitor of CD221. Overexpression of CD221 increased colony-forming ability. We also found that inhibition of CD340 (erbB2) and CD266 (fibroblast growth factor-inducible 14) signals suppressed proliferation. In addition, both insulin-like growth factor (a ligand of CD221) and tumor necrosis factor-like weak inducer of apoptosis (a ligand of CD266) were provided by feeder cells in our culture system. This study revealed the expression profiles of cell surface molecules in human iPS cell-derived HPCs and that the paracrine interactions between HPCs and other cells through specific receptors are important for proliferation.
|
| Volume |
24(14)
|
| Pages |
1691-702
|
| Published |
2015-7-15
|
| DOI |
10.1089/scd.2014.0479
|
| PMID |
25808356
|
| PMC |
PMC4499795
|
| MeSH |
3T3 Cells
Animals
Bile Ducts / cytology*
Biomarkers / metabolism
Cell Culture Techniques
Cell Differentiation
Cell Line
Cell Proliferation
Cytokines / pharmacology
Feeder Cells / metabolism
Fibroblast Growth Factors / antagonists & inhibitors
Flow Cytometry
Hepatocytes / cytology*
Humans
Induced Pluripotent Stem Cells / cytology*
Membrane Proteins / metabolism*
Mice
Receptor, ErbB-2 / antagonists & inhibitors
Receptor, IGF Type 1 / biosynthesis
Receptors, Somatomedin / antagonists & inhibitors
Receptors, Somatomedin / immunology
Receptors, Somatomedin / metabolism
Receptors, Tumor Necrosis Factor / metabolism
Somatomedins / metabolism
TWEAK Receptor
|
| IF |
3.153
|
| Times Cited |
11
|
|
WOS Category
|
MEDICINE, RESEARCH & EXPERIMENTAL
TRANSPLANTATION
HEMATOLOGY
CELL & TISSUE ENGINEERING
|
| Resource |
| Human and Animal Cells |
HiPS-RIKEN-2F(HPS0014) |
