title: Efficient and directive generation of two distinct endoderm lineages from human ESCs and iPSCs by differentiation stage-specific SOX17 transduction.
abstract: The establishment of methods for directive differentiation from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) is important for regenerative medicine. Although Sry-related HMG box 17 (SOX17) overexpression in ESCs leads to differentiation of either extraembryonic or definitive endoderm cells, respectively, the mechanism of these distinct results remains unknown. Therefore, we utilized a transient adenovirus vector-mediated overexpression system to mimic the SOX17 expression pattern of embryogenesis. The number of alpha-fetoprotein-positive extraembryonic endoderm (ExEn) cells was increased by transient SOX17 transduction in human ESC- and iPSC-derived primitive endoderm cells. In contrast, the number of hematopoietically expressed homeobox (HEX)-positive definitive endoderm (DE) cells, which correspond to the anterior DE in vivo, was increased by transient adenovirus vector-mediated SOX17 expression in human ESC- and iPSC-derived mesendoderm cells. Moreover, hepatocyte-like cells were efficiently generated by sequential transduction of SOX17 and HEX. Our findings show that a stage-specific transduction of SOX17 in the primitive endoderm or mesendoderm promotes directive ExEn or DE differentiation by SOX17 transduction, respectively.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takayama
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Inamura
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawabata
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Tashiro
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Katayama
authors.forename: Fuminori
authors.initials: F
authors.lastname: Sakurai
authors.forename: Takao
authors.initials: T
authors.lastname: Hayakawa
authors.forename: Miho Kusuda
authors.initials: MK
authors.lastname: Furue
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizuguchi
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D004707:Endoderm / Q000166:cytology*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D008099:Liver / Q000166:cytology; D008648:Mesoderm / Q000166:cytology; D055760:SOXF Transcription Factors / Q000378:metabolism*; D014161:Transduction, Genetic
chemical_list: D018398:Homeodomain Proteins; C109188:SOX17 protein, human; D055760:SOXF Transcription Factors