title: Spontaneously differentiated GATA6-positive human embryonic stem cells represent an important cellular step in human embryonic development; they are not just an artifact of in vitro culture.
abstract: In this study, we isolated and characterized spontaneously differentiated human embryonic stem cells (SD-hESCs) found in hESC colonies in comparison to the morphologically premature ESCs in the colonies to investigate the potential role of SD-hESCs in embryogenesis. SD-hESCs were distinguished from undifferentiated hESCs by their higher expression of GATA6, a marker for primitive endoderm and transthyretin, a marker visceral endoderm in embryoid bodies (EBs). SD-hESCs expressed OCT4 and NANOG, markers for pluripotent stem cells, at significantly lower levels than undifferentiated hESCs. EBs derived from isolated SD-hESCs were morphologically distinct from cells directly derived from the undifferentiated hESCs; they contained higher number of cysts compared to EBs from undifferentiated hESC-derived EBs (42% vs. 20%). Furthermore, the extracellular signal molecule, BMP2/4, induced a higher GATA4/6 expression and cystic EB formation than control and noggin-treated EBs. Since cystic formation in EBs play a role in primitive endoderm formation during embryogenesis, the SD-hESC may be a relevant cell type equipped to differentiate into primitive endoderm. Our results suggest that SD-ESCs generated during routine hESC culture are not just an artifact of in vitro culture and these cells could serve as a useful model to study the process of embryogenesis.
authors.affiliation: 1 Department of Biomedical Science, Graduate School of Biomedical Science and Engineering, Hanyang University , Seoul, Korea.
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Ki Sung
authors.initials: KS
authors.lastname: Hong
authors.forename: Charlie
authors.initials: C
authors.lastname: Mantel
authors.forename: Hal E
authors.initials: HE
authors.lastname: Broxmeyer
authors.forename: Man Ryul
authors.initials: MR
authors.lastname: Lee
authors.forename: Kye-Seong
authors.initials: KS
authors.lastname: Kim
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D047108:Embryonic Development / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004707:Endoderm / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D050993:GATA6 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D011228:Prealbumin / Q000235:genetics / Q000378:metabolism; D000099176:Noggin Protein
chemical_list: D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D002352:Carrier Proteins; D050993:GATA6 Transcription Factor; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D011228:Prealbumin; D000099176:Noggin Protein; C525718:BMP2 protein, human; C525809:BMP4 protein, human; C494759:GATA6 protein, human; C486780:NANOG protein, human; C494173:POU5F1 protein, human