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

Tohru Kimura, Yoshiaki Kaga, Hiroshi Ohta, Mika Odamoto, Yoichi Sekita, Kunpeng Li, Noriko Yamano, Keita Fujikawa, Ayako Isotani, Norihiko Sasaki, Masashi Toyoda, Katsuhiko Hayashi, Masaru Okabe, Takashi Shinohara, Mitinori Saitou, Toru Nakano

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2668-2678
Number of pages11
JournalSTEM CELLS
Volume32
Issue number10
DOIs
Publication statusPublished - Jan 1 2014
Externally publishedYes

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Extracellular Signal-Regulated MAP Kinases
Germ Cells
Down-Regulation
Feeder Cells
Pluripotent Stem Cells
Gastrulation
Bone Morphogenetic Proteins
Mouse Embryonic Stem Cells
DNA Methylation
Coculture Techniques
Tretinoin
Genes
Phosphotransferases

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Kimura, T., Kaga, Y., Ohta, H., Odamoto, M., Sekita, Y., Li, K., ... Nakano, T. (2014). Induction of primordial germ cell-like cells from mouse embryonic stem cells by ERK signal inhibition. STEM CELLS, 32(10), 2668-2678. https://doi.org/10.1002/stem.1781

Induction of primordial germ cell-like cells from mouse embryonic stem cells by ERK signal inhibition. / Kimura, Tohru; Kaga, Yoshiaki; Ohta, Hiroshi; Odamoto, Mika; Sekita, Yoichi; Li, Kunpeng; Yamano, Noriko; Fujikawa, Keita; Isotani, Ayako; Sasaki, Norihiko; Toyoda, Masashi; Hayashi, Katsuhiko; Okabe, Masaru; Shinohara, Takashi; Saitou, Mitinori; Nakano, Toru.

In: STEM CELLS, Vol. 32, No. 10, 01.01.2014, p. 2668-2678.

Research output: Contribution to journalArticle

Kimura, T, Kaga, Y, Ohta, H, Odamoto, M, Sekita, Y, Li, K, Yamano, N, Fujikawa, K, Isotani, A, Sasaki, N, Toyoda, M, Hayashi, K, Okabe, M, Shinohara, T, Saitou, M & Nakano, T 2014, 'Induction of primordial germ cell-like cells from mouse embryonic stem cells by ERK signal inhibition', STEM CELLS, vol. 32, no. 10, pp. 2668-2678. https://doi.org/10.1002/stem.1781
Kimura, Tohru ; Kaga, Yoshiaki ; Ohta, Hiroshi ; Odamoto, Mika ; Sekita, Yoichi ; Li, Kunpeng ; Yamano, Noriko ; Fujikawa, Keita ; Isotani, Ayako ; Sasaki, Norihiko ; Toyoda, Masashi ; Hayashi, Katsuhiko ; Okabe, Masaru ; Shinohara, Takashi ; Saitou, Mitinori ; Nakano, Toru. / Induction of primordial germ cell-like cells from mouse embryonic stem cells by ERK signal inhibition. In: STEM CELLS. 2014 ; Vol. 32, No. 10. pp. 2668-2678.
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