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

Jun Ho Lee, Ki Sung Hong, Charlie Mantel, Hal E. Broxmeyer, Man Ryul Lee, Kye Seong Kim

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2706-2713
Number of pages8
JournalStem cells and development
Volume22
Issue number20
DOIs
StatePublished - Oct 15 2013

ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology

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