Protein kinase C mediated extraembryonic endoderm differentiation of human embryonic stem cells.
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.
Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, WI, USA.
Xuezhu
X
Feng
Jiuchun
J
Zhang
Kimberly
K
Smuga-Otto
Shulan
S
Tian
Junying
J
Yu
Ron
R
Stewart
James A
JA
Thomson
D000943:Antigens, Differentiation / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D015536:Down-Regulation; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000502:physiology*; D004707:Endoderm / Q000166:cytology*; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition; D020869:Gene Expression Profiling; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism / Q000502:physiology; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000943:Antigens, Differentiation; D020536:Enzyme Activators; D007527:Isoenzymes; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate