title: Expression of coagulation factors from murine induced pluripotent stem cell-derived liver cells.
abstract: A protocol to differentiate liver cells from induced pluripotent stem (iPS) cells is being established. However, the ability of these differentiated iPS cells to express liver-specific proteins, such as coagulation cascade and related factors, has yet to be assessed. This study evaluated whether liver-like populations differentiated from murine iPS cells gain the ability to produce coagulation-related factors. Following differentiation of murine iPS cells into hematopoietic-like and liver-like embryoid bodies, we assessed gene expression profiles for coagulation-related markers, including fibrinogen, factors II, V, VII, VIII, IX, X, XI, XII, and XIIIβ, protein C, protein S, antithrombin, plasminogen, von Willebrand factor, and ADAMTS13 by real-time reverse transcription PCR. Liver-like embryoid bodies demonstrated strong expression levels of nearly all the coagulation-related genes assessed, compared with undifferentiated iPS cells and hematopoietic-like embryoid bodies. We also confirmed efficient translation and secretion of fibrinogen and albumin (hepatocyte-specific marker proteins) into the conditioned medium by these differentiated cells, suggesting successful differentiation of iPS cells into the liver lineage. These findings suggest that iPS cells can be differentiated into liver-like populations that express coagulation-related factors. Liver-like embryoid bodies may provide a source for cell-based therapies directed toward liver diseases, including coagulation factor deficiencies in the future.
authors.affiliation: Department of Legal Medicine, Nara Medical University School of Medicine, 840 Shijo-cho, Kashihara, Nara.
authors.forename: Shogo
authors.initials: S
authors.lastname: Kasuda
authors.forename: Kohei
authors.initials: K
authors.lastname: Tatsumi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Sakurai
authors.forename: Junko
authors.initials: J
authors.lastname: Kato
authors.forename: Sanae
authors.initials: S
authors.lastname: Taminishi
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Takeda
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ohashi
authors.forename: Teruo
authors.initials: T
authors.lastname: Okano
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Hatake
authors.forename: Midori
authors.initials: M
authors.lastname: Shima
mesh_terms: D000071120:ADAMTS13 Protein; D000818:Animals; D000991:Antithrombins / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis*; D001778:Blood Coagulation Disorders / Q000097:blood* / Q000503:physiopathology / Q000628:therapy; D001779:Blood Coagulation Factors / Q000235:genetics / Q000378:metabolism*; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002460:Cell Line; D058732:Embryoid Bodies / Q000166:cytology / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D058990:Molecular Targeted Therapy; D011486:Protein C / Q000235:genetics / Q000378:metabolism; D017293:Protein S / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D033581:Stem Cell Transplantation
chemical_list: D000991:Antithrombins; D015415:Biomarkers; D001779:Blood Coagulation Factors; D011486:Protein C; D017293:Protein S; D012333:RNA, Messenger; C502939:ADAMTS13 protein, mouse; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein