title: Oncostatin M in William's E medium is suitable for initiation of hepatocyte differentiation in human induced pluripotent stem cells.
abstract: William's E (WE) is a suitable medium for the differentiation of human induced pluripotent stem (iPS) cells to the hepatocyte lineage. The aim of the present study was to investigate various growth factors in their ability to promote hepatocyte differentiation of iPS cells in WE medium. Human iPS 201B7 cells were cultured in WE medium supplemented with growth factors, and mRNA expression levels and promoter activities of α‑fetoprotein (AFP) and albumin were examined by reverse transcription‑quantitative polymerase chain reaction and luciferase assay, respectively. In addition, time course analysis of AFP mRNA expression was performed in 201B7 cells cultured in WE medium supplemented with oncostatin M. The results demonstrated that mRNA expression levels of AFP were significantly elevated by most growth factors tested as supplements in WE medium, except all‑trans retinoic acid, compared with cells cultured in ReproFF (a medium that maintains pluripotency). The highest increase in AFP mRNA expression levels was observed by oncostatin M stimulation. Albumin mRNA expression levels were increased by all‑trans retinoic acid and insulin‑transferrin‑selenium supplementation in WE medium compared with cells cultured in ReproFF. Oncostatin M supplementation significantly stimulated the promoter activity of the AFP gene, but no growth factor tested significantly stimulated the promoter activity of the albumin gene. By time course analysis, significant increase of AFP mRNA expression was observed on the sixth day post‑stimulation, compared with cells cultured in WE medium alone. In conclusion, the present study demonstrated that oncostatin M supplementation in WE medium was sufficient to initiate hepatocyte differentiation in iPS cells.
authors.affiliation: Department of Gastroenterology, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284‑0003, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Tomizawa
authors.affiliation: Department of Radiology, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284‑0003, Japan.
authors.forename: Fuminobu
authors.initials: F
authors.lastname: Shinozaki
authors.affiliation: Department of Neurology, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284‑0003, Japan.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Motoyoshi
authors.affiliation: Department of Rheumatology, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284‑0003, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Sugiyama
authors.affiliation: Department of Pediatrics, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284‑0003, Japan.
authors.forename: Shigenori
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Department of Neurosurgery, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284‑0003, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishige
mesh_terms: D000418:Albumins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002478:Cells, Cultured; D003470:Culture Media; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects*; D053683:Oncostatin M / Q000494:pharmacology*; D019188:Organ Preservation Solutions / Q000737:chemistry*; D012333:RNA, Messenger / Q000096:biosynthesis; D014212:Tretinoin / Q000494:pharmacology; D000509:alpha-Fetoproteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: D000418:Albumins; D003470:Culture Media; D019188:Organ Preservation Solutions; D012333:RNA, Messenger; C475563:William's medium E; D000509:alpha-Fetoproteins; D053683:Oncostatin M; D014212:Tretinoin; D017228:Hepatocyte Growth Factor