Induction of mouse germ-cell fate by transcription factors in vitro

Fumio Nakaki, Katsuhiko Hayashi, Hiroshi Ohta, Kazuki Kurimoto, Yukihiro Yabuta, Mitinori Saitou

Research output: Contribution to journalArticle

160 Citations (Scopus)

Abstract

The germ-cell lineage ensures the continuity of life through the generation of male and female gametes, which unite to form a totipotent zygote. We have previously demonstrated that, by using cytokines, embryonic stem cells and induced pluripotent stem cells can be induced into epiblast-like cells (EpiLCs) and then into primordial germ cell (PGC)-like cells with the capacity for both spermatogenesis and oogenesis, creating an opportunity for understanding and regulating mammalian germ-cell development in both sexes in vitro. Here we show that, without cytokines, simultaneous overexpression of three transcription factors, Blimp1 (also known as Prdm1), Prdm14 and Tfap2c (also known as AP2γ), directs EpiLCs, but not embryonic stem cells, swiftly and efficiently into a PGC state. Notably, Prdm14 alone, but not Blimp1 or Tfap2c, suffices for the induction of the PGC state in EpiLCs. The transcription-factor- induced PGC state, irrespective of the transcription factors used, reconstitutes key transcriptome and epigenetic reprogramming in PGCs, but bypasses a mesodermal program that accompanies PGC or PGC-like-cell specification by cytokines including bone morphogenetic protein 4. Notably, the transcription-factor-induced PGC-like cells contribute to spermatogenesis and fertile offspring. Our findings provide a new insight into the transcriptional logic for PGC specification, and create a foundation for the transcription-factor-based reconstitution and regulation of mammalian gametogenesis.

Original languageEnglish
Pages (from-to)222-226
Number of pages5
JournalNature
Volume501
Issue number7466
DOIs
Publication statusPublished - Aug 8 2013
Externally publishedYes

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Germ Cells
Transcription Factors
Germ Layers
Spermatogenesis
Embryonic Stem Cells
Cytokines
In Vitro Techniques
Bone Morphogenetic Protein 4
Gametogenesis
Induced Pluripotent Stem Cells
Oogenesis
Zygote
Cell Lineage
Transcriptome
Epigenomics

All Science Journal Classification (ASJC) codes

  • General

Cite this

Nakaki, F., Hayashi, K., Ohta, H., Kurimoto, K., Yabuta, Y., & Saitou, M. (2013). Induction of mouse germ-cell fate by transcription factors in vitro. Nature, 501(7466), 222-226. https://doi.org/10.1038/nature12417

Induction of mouse germ-cell fate by transcription factors in vitro. / Nakaki, Fumio; Hayashi, Katsuhiko; Ohta, Hiroshi; Kurimoto, Kazuki; Yabuta, Yukihiro; Saitou, Mitinori.

In: Nature, Vol. 501, No. 7466, 08.08.2013, p. 222-226.

Research output: Contribution to journalArticle

Nakaki, F, Hayashi, K, Ohta, H, Kurimoto, K, Yabuta, Y & Saitou, M 2013, 'Induction of mouse germ-cell fate by transcription factors in vitro', Nature, vol. 501, no. 7466, pp. 222-226. https://doi.org/10.1038/nature12417
Nakaki F, Hayashi K, Ohta H, Kurimoto K, Yabuta Y, Saitou M. Induction of mouse germ-cell fate by transcription factors in vitro. Nature. 2013 Aug 8;501(7466):222-226. https://doi.org/10.1038/nature12417
Nakaki, Fumio ; Hayashi, Katsuhiko ; Ohta, Hiroshi ; Kurimoto, Kazuki ; Yabuta, Yukihiro ; Saitou, Mitinori. / Induction of mouse germ-cell fate by transcription factors in vitro. In: Nature. 2013 ; Vol. 501, No. 7466. pp. 222-226.
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