TY - JOUR
T1 - Protein kinase C mediated extraembryonic endoderm differentiation of human embryonic stem cells
AU - Feng, Xuezhu
AU - Zhang, Jiuchun
AU - Smuga-Otto, Kimberly
AU - Tian, Shulan
AU - Yu, Junying
AU - Stewart, Ron
AU - Thomson, James A.
PY - 2012/3
Y1 - 2012/3
N2 - 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.
AB - 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.
KW - Extraembryonic endoderm
KW - Human embryonic stem cells
KW - PKC
KW - TPA
UR - http://www.scopus.com/inward/record.url?scp=84863120939&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863120939&partnerID=8YFLogxK
U2 - 10.1002/stem.1018
DO - 10.1002/stem.1018
M3 - Article
C2 - 22213079
AN - SCOPUS:84863120939
SN - 1066-5099
VL - 30
SP - 461
EP - 470
JO - Stem Cells
JF - Stem Cells
IS - 3
ER -