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Stem Cells. 2014 Oct;32(10):2668-78. doi: 10.1002/stem.1781.

Induction of primordial germ cell-like cells from mouse embryonic stem cells by ERK signal inhibition.

Author information

1
Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan; Department of Pathology, Medical School, Osaka University, Suita, Osaka, Japan; Laboratory of Molecular Embryology, Department of Biosciences, Kitasato University School of Science, Kitasato, Minami-ku, Sagamihara, Kanagawa, Japan; Laboratory of Stem Cell Biology, Department of Biosciences, Kitasato University School of Science, Kitasato, Minami-ku, Sagamihara, Kanagawa, Japan.

Abstract

Primordial germ cells (PGCs) are embryonic germ cell precursors. Specification of PGCs occurs under the influence of mesodermal induction signaling during in vivo gastrulation. Although bone morphogenetic proteins and Wnt signaling play pivotal roles in both mesodermal and PGC specification, the signal regulating PGC specification remains unknown. Coculture of mouse embryonic stem cells (ESCs) with OP9 feeder cells induces mesodermal differentiation in vitro. Using this mesodermal differentiation system, we demonstrated that PGC-like cells were efficiently induced from mouse ESCs by extracellular signal-regulated kinase (ERK) signaling inhibition. Inhibition of ERK signaling by a MAPK/ERK kinase (MEK) inhibitor upregulated germ cell marker genes but downregulated mesodermal genes. In addition, the PGC-like cells showed downregulation of DNA methylation and formed pluripotent stem cell colonies upon treatment with retinoic acid. These results show that inhibition of ERK signaling suppresses mesodermal differentiation but activates germline differentiation program in this mesodermal differentiation system. Our findings provide a new insight into the signaling networks regulating PGC specification.

KEYWORDS:

ERK signal; Embryonic stem cells; In vitro differentiation; Mesoderm; Primordial germ cells

PMID:
24989326
DOI:
10.1002/stem.1781
[Indexed for MEDLINE]
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