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

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number182
JournalBiology of Reproduction
Volume86
Issue number6
DOIs
Publication statusPublished - Jun 1 2012
Externally publishedYes

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Pluripotent Stem Cells
Germ Cells
Mitogen-Activated Protein Kinase Kinases
Gene Expression Profiling
S Phase
Transcriptome
Transforming Growth Factor beta
Cell Cycle
Flow Cytometry
Genes

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Tracing the conversion process from primordial germ cells to pluripotent stem cells in mice. / Nagamatsu, Go; Kosaka, Takeo; Saito, Shigeru; Takubo, Keiyo; Akiyama, Hideo; Sudo, Tetsuo; Horimoto, Katsuhisa; Oya, Mototsugu; Suda, Toshio.

In: Biology of Reproduction, Vol. 86, No. 6, 182, 01.06.2012.

Research output: Contribution to journalArticle

Nagamatsu, G, Kosaka, T, Saito, S, Takubo, K, Akiyama, H, Sudo, T, Horimoto, K, Oya, M & Suda, T 2012, 'Tracing the conversion process from primordial germ cells to pluripotent stem cells in mice', Biology of Reproduction, vol. 86, no. 6, 182. https://doi.org/10.1095/biolreprod.111.096792
Nagamatsu, Go ; Kosaka, Takeo ; Saito, Shigeru ; Takubo, Keiyo ; Akiyama, Hideo ; Sudo, Tetsuo ; Horimoto, Katsuhisa ; Oya, Mototsugu ; Suda, Toshio. / Tracing the conversion process from primordial germ cells to pluripotent stem cells in mice. In: Biology of Reproduction. 2012 ; Vol. 86, No. 6.
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