Induction of Primordial Germ Cell-Like Cells From Mouse Embryonic Stem Cells by ERK Signal Inhibition

被引：31

作者：

Kimura, Tohru ^{[1
,2
,4
,5
]}

Kaga, Yoshiaki ^{[1
]}

Ohta, Hiroshi ^{[6
]}

Odamoto, Mika ^{[4
,5
]}

Sekita, Yoichi ^{[2
]}

Li, Kunpeng ^{[1
]}

Yamano, Noriko ^{[1
]}

Fujikawa, Keita ^{[4
,5
]}

Isotani, Ayako ^{[3
]}

Sasaki, Norihiko ^{[8
]}

Toyoda, Masashi ^{[8
]}

Hayashi, Katsuhiko ^{[6
,9
]}

Okabe, Masaru ^{[3
]}

Shinohara, Takashi ^{[7
]}

Saitou, Mitinori ^{[6
,10
,11
,12
]}

Nakano, Toru ^{[1
,2
,13
]}

机构：

[1] Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka, Japan

[2] Osaka Univ, Sch Med, Dept Pathol, Suita, Osaka 565, Japan

[3] Osaka Univ, Microbial Dis Res Inst, Suita, Osaka 565, Japan

[4] Kitasato Univ, Sch Sci, Lab Mol Embryol, Minami Ku, Sagamihara, Kanagawa 2520373, Japan

[5] Kitasato Univ, Sch Sci, Dept Biosci, Lab Stem Cell Biol,Minami Ku, Sagamihara, Kanagawa 2520373, Japan

[6] Kyoto Univ, Dept Anat & Cell Biol, Sakyo Ku, Kyoto, Japan

[7] Kyoto Univ, Dept Mol Genet, Grad Sch Med, Sakyo Ku, Kyoto, Japan

[8] Tokyo Metropolitan Inst Gerontol, Res Team Geriatr Med Vasc Med, Itabashi Ku, Tokyo, Japan

[9] Precursory Res Embryon Sci & Technol PRESTO, Tokyo, Japan

[10] Japan Sci & Technol Agcy JST, Exploratory Res Adv Technol ERATO, Sakyo Ku, Kyoto, Japan

[11] Kyoto Univ, Ctr iPS Cell Res & Applicat, Sakyo Ku, Kyoto, Japan

[12] Kyoto Univ, Inst Integrated Cell Mat Sci, Sakyo Ku, Kyoto, Japan

[13] Core Res Evolut Sci & Technol CREST, JST, Chiyoda Ku, Tokyo, Japan

来源：

STEM CELLS | 2014年 / 32卷 / 10期

关键词：

Primordial germ cells; In vitro differentiation; Embryonic stem cells; Mesoderm; ERK signal; IN-VITRO; MESODERM FORMATION; AXIS FORMATION; MICE; SPECIFICATION; GENERATION; LINEAGE; FATE; DIFFERENTIATION; REQUIREMENT;

D O I：

10.1002/stem.1781

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：2668 / 2678

页数：11

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