Lee, Jun HoHong, Ki SungMantel, CharlieBroxmeyer, Hal E.Lee, Man RyulKim, Kye-Seong2015-11-032015-11-032013-10-15Lee, J. H., Hong, K. S., Mantel, C., Broxmeyer, H. E., Lee, M. R., & Kim, K.-S. (2013). 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. Stem Cells and Development, 22(20), 2706–2713. http://doi.org/10.1089/scd.2013.0083https://hdl.handle.net/1805/7328In 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.en-USPublisher PolicyStem-cell differentiationHuman embryonic stem cellsGene Expression Regulation, DevelopmentalEmbryonic DevelopmentGATA6 Transcription FactorSpontaneously induced differentiating cellsArticle