Open AccessProtein Kinase C Mediated Extraembryonic Endoderm Differentiation of Human Embryonic Stem Cells
Author(s) -
Feng Xuezhu,
Zhang Jiuchun,
SmugaOtto Kimberly,
Tian Shulan,
Yu Junying,
Stewart Ron,
Thomson James A.
Publication year - 2012
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1018
Subject(s) - ectoderm , endoderm , biology , germ layer , microbiology and biotechnology , embryonic stem cell , stem cell , cellular differentiation , protein kinase c , embryogenesis , embryo , kinase , genetics , induced pluripotent stem cell , gene
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. S TEM C ELLS 2012;30:461–470