Transcription factor-mediated germ cell induction in rats reveals ETV4 cooperates with germline specifiers
The specification of primordial germ cells (PGCs) marks a crucial branchpoint in early embryonic development. Studying the molecular mechanisms governing this process is crucial for understanding reproduction and evolution. Here, we identify transcription factors essential for PGC specification in rats using an in vitro system to induce PGC-like cells (PGCLCs) from pluripotent cells. Overexpression of Tbxt, a key mesodermal factor activating the germ cell program in epiblast-like cells, induces functional rat PGCLCs, similar to mice. However, unlike in mice, overexpression of the PGC specifiers (Prdm14, Blimp1, and Ap2γ) alone is not sufficient in rats; additional Activin and WNT signals are necessary for PGCLC induction. Through a candidate screen, we identified the transcription factor Etv4 acting cooperatively with the three PGC specifiers. Our study provides insight into the mechanism behind germline segregation in mammals and underscores the importance of using the rat model in addition to mice.
Authors
- Takuya Yamamoto (ORCID: https://orcid.org/0000-0002-0022-3947)
- Hisato Kobayashi (ORCID: https://orcid.org/0000-0003-3800-4691)
- Toshihiro Kobayashi (ORCID: https://orcid.org/0000-0001-8019-0008)
- Kazuki Kurimoto (ORCID: https://orcid.org/0000-0003-0206-414X)
- Hiroshi Saito (ORCID: https://orcid.org/0000-0002-3338-478X)
- Kenyu Iwatsuki (ORCID: https://orcid.org/0000-0003-0645-9819)
- Hiroki Kojima (ORCID: https://orcid.org/0000-0002-8894-1694)
- Masumi Hirabayashi (ORCID: https://orcid.org/0000-0002-1059-5883)
- Mami Oikawa
- Makoto Sanbo (ORCID: https://orcid.org/0000-0001-8806-1745)
- Tomoyuki Yamaguchi (ORCID: https://orcid.org/0000-0002-3070-2885)
- K Nishioka
Institutions
- Tokyo University of Pharmacy and Life Sciences (JP)
- National Institutes of Natural Sciences (JP)
- Kyoto University (JP)
- National Institute for Physiological Sciences (JP)
- Nara Medical University (JP)
- The University of Tokyo (JP)
- Dokkyo Medical University (JP)
Publication Details
- Journal
- Stem Cell Reports
- Published
- 2025-08-01
- DOI
- https://doi.org/10.1016/j.stemcr.2025.102599
- Primary Topic
- Pluripotent Stem Cells Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Sumitomo Foundation
- Japan Agency for Medical Research and Development
- Ministry of Education, Culture, Sports, Science and Technology
- Kato Memorial Bioscience Foundation
- Daiichi Sankyo Foundation of Life Science
- Japan Society for the Promotion of Science
- Japan Science and Technology Agency
- National Institute for Physiological Sciences