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Updated: Sep 11, 2025

Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
Published on: June 21, 2016
Transcription factor-mediated germ cell induction in rats reveals ETV4 cooperates with germline specifiers
Mami Oikawa1, Hiroki Kojima2, Hisato Kobayashi3
1Division of Mammalian Embryology, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan; Laboratory of Regenerative Medicine, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo 192-0392, Japan.
Abstract:
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.
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