Oikawa Mami, Kojima Hiroki, Kobayashi Hisato, Iwatsuki Kenyu, Saito Hijiri, Sanbo Makoto, Nishioka Kazumi, Yamaguchi Tomoyuki, Yamamoto Takuya, Kurimoto Kazuki, Hirabayashi Masumi, Kobayashi Toshihiro
Division 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.
Division 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; Division of Mammalian Embryogenesis, Department of Homeostatic Regulation, National Institute for Physiological Sciences, Okazaki, Aichi 444-8787, Japan.
Stem Cell Reports. 2025 Aug 12;20(8):102599. doi: 10.1016/j.stemcr.2025.102599.
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.
原始生殖细胞（PGCs）的特化标志着早期胚胎发育中的一个关键分支点。研究控制这一过程的分子机制对于理解生殖和进化至关重要。在这里，我们使用体外系统从多能细胞诱导产生类原始生殖细胞（PGCLCs），从而确定大鼠中PGC特化所必需的转录因子。激活上胚层样细胞中生殖细胞程序的关键中胚层因子Tbxt的过表达，可诱导出功能性大鼠PGCLCs，类似于小鼠。然而，与小鼠不同的是，仅PGC特化因子（Prdm14、Blimp1和Ap2γ）的过表达在大鼠中并不足够；PGCLC诱导还需要额外的激活素和WNT信号。通过候选筛选，我们确定了转录因子Etv4与这三个PGC特化因子协同作用。我们的研究深入了解了哺乳动物种系分离背后的机制，并强调了除小鼠外使用大鼠模型的重要性。
