Protein kinase C mediated extraembryonic endoderm differentiation of human embryonic stem cells

Xuezhu Feng, Jiuchun Zhang, Kimberly Smuga-Otto, Shulan Tian, Junying Yu, Ron Stewart, James A. Thomson

Research output: Contribution to journalArticlepeer-review


Unlike mouse embryonic stem cells (ESCs), which are closely related to the inner cell mass, human ESCs appear to be more closely related to the later primitive ectoderm. For example, human ESCs and primitive ectoderm share a common epithelial morphology, growth factor requirements, and the potential to differentiate to all three embryonic germ layers. However, it has previously been shown that human ESCs can also differentiate to cells expressing markers of trophoblast, an extraembryonic lineage formed before the formation of primitive ectoderm. Here, we show that phorbol ester 12-O-tetradecanoylphorbol 13-acetate causes human ESCs to undergo an epithelial mesenchymal transition and to differentiate into cells expressing markers of parietal endoderm, another extraembryonic lineage. We further confirmed that this differentiation is through the activation of protein kinase C (PKC) pathway and demonstrated that a particular PKC subtype, PKC-δ, is most responsible for this transition.

Original languageEnglish (US)
Pages (from-to)461-470
Number of pages10
JournalStem Cells
Issue number3
StatePublished - Mar 2012


  • Extraembryonic endoderm
  • Human embryonic stem cells
  • PKC
  • TPA

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology


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