Tracing the conversion process from primordial germ cells to pluripotent stem cells in mice

Go Nagamatsu, Takeo Kosaka, Shigeru Saito, Keiyo Takubo, Hideo Akiyama, Tetsuo Sudo, Katsuhisa Horimoto, Mototsugu Oya, Toshio Suda

研究成果: Article査読

13 被引用数 (Scopus)

抄録

To understand mechanisms underlying acquisition of pluripotency, it is critical to identify cells that can be converted to pluripotent stem cells. For this purpose, we focused on unipotent primordial germ cells (PGCs), which can be reprogrammed into pluripotent embryonic germ (EG) cells under defined conditions. Treatment of PGCs with combinations of signaling inhibitors, including inhibitors of MAP2K (MEK), GSK3B (GSK-3beta), and TGFB (TGFbeta) type 1 receptors, induced cells to enter a pluripotent state at a high frequency (12.1%) by Day 10 of culture. When we employed fluorescence-activated cell sorting to monitor conversion of candidate cells to a pluripotent state, we observed a cell cycle shift to S phase, indicating enrichment of pluripotent cells, during the early phase of EG formation. Transcriptome analysis revealed that PGCs retained expression of some pluripotent stem cell-associated genes, such as Pou5f1 and Sox2, during EG cell formation. On the other hand, PGCs lost their germ lineage characteristics and acquired expression of pluripotent stem cell markers, such as Klf4 and Eras. The overall gene expression profiles revealed by this system provide novel insight into how pluripotency is acquired in germcommitted cells.

本文言語English
論文番号182
ジャーナルBiology of reproduction
86
6
DOI
出版ステータスPublished - 2012 6 1

ASJC Scopus subject areas

  • 生殖医学
  • 細胞生物学

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