Transcription factor-mediated germ cell induction in rats reveals ETV4 cooperates with germline specifiers.

IF 5.1 2区医学 Q1 CELL & TISSUE ENGINEERING

Stem Cell Reports Pub Date : 2025-08-12 DOI:10.1016/j.stemcr.2025.102599

Mami Oikawa, Hiroki Kojima, Hisato Kobayashi, Kenyu Iwatsuki, Hijiri Saito, Makoto Sanbo, Kazumi Nishioka, Tomoyuki Yamaguchi, Takuya Yamamoto, Kazuki Kurimoto, Masumi Hirabayashi, Toshihiro Kobayashi

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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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转录因子介导的大鼠生殖细胞诱导揭示了ETV4与种系指示物的协同作用。

原始生殖细胞（PGCs）的分化标志着早期胚胎发育的一个关键分支点。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，我们利用体外系统从多能细胞诱导PGC样细胞（pgclc），确定了大鼠PGC规范所必需的转录因子。Tbxt是一种在上皮样细胞中激活生殖细胞程序的关键中胚层因子，其过表达可诱导与小鼠类似的功能性大鼠pgclc。然而，与小鼠不同，PGC指示物（Prdm14、Blimp1和Ap2γ）单独过表达在大鼠中是不够的；额外的激活素和WNT信号对于PGCLC的诱导是必需的。通过候选筛选，我们确定了转录因子Etv4与三种PGC指示物协同作用。我们的研究为哺乳动物种系分离背后的机制提供了见解，并强调了除小鼠外使用大鼠模型的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY

CiteScore

10.50

自引率

1.70%

发文量

200

审稿时长

28 weeks

期刊介绍： Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.