Efficient and directive generation of two distinct endoderm lineages from human ESCs and iPSCs by differentiation stage-specific SOX17 transduction

• Published in: PloS one Vol. 6; no. 7; p. e21780
• Main Authors: Takayama, Kazuo, Inamura, Mitsuru, Kawabata, Kenji, Tashiro, Katsuhisa, Katayama, Kazufumi, Sakurai, Fuminori, Hayakawa, Takao, Furue, Miho Kusuda, Mizuguchi, Hiroyuki
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.07.2011; Public Library of Science (PLoS)
• Subjects: Adenoviridae - metabolism; Adenoviruses; Adipocytes; Biochemistry; Biology; Cell Differentiation; Cell Line; Cell Lineage; Differentiation; Embryo cells; Embryogenesis; Embryonic development; Embryonic growth stage; Embryonic stem cells; Embryonic Stem Cells - cytology; Embryonic Stem Cells - metabolism; Embryos; Endoderm; Endoderm - cytology; Genes; Glycoproteins; Homeobox; Homeodomain Proteins - metabolism; Humans; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - metabolism; Laboratories; Liver - cytology; Mesendoderm; Mesoderm - cytology; Molecular biology; Pharmaceutical sciences; Physiology; Pluripotency; Polypeptides; Regenerative medicine; SOXF Transcription Factors - metabolism; Stem cells; Transcription factors; Transduction, Genetic; α-Fetoprotein; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0021780

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.