Yu Honglin, Wang Ziqi, Ma Jiayue, Wang Ruoming, Yao Shuo, Gu Zhaoyu, Lin Kexin, Li Jinlan, Young Robert S, Yu Ya, Yu You, Jin Min, Chen Di
Center for Reproductive Medicine of The Second Affiliated Hospital, Center for Regeneration and Cell Therapy of Zhejiang, University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Haining, 314400, Zhejiang, China.
College of Animal & Veterinary Sciences, Southwest Minzu University, Chengdu, 610041, Sichuan, China.
Stem Cell Res Ther. 2025 Mar 18;16(1):139. doi: 10.1186/s13287-025-04171-2.
The specification of primordial germ cells (PGCs) during early embryogenesis initiates the development of the germ cell lineage that ensures the perpetuation of genetic and epigenetic information from parents to offspring. Defects in germ cell development may lead to infertility or birth defects. Historically, our understanding of human PGCs (hPGCs) regulation has primarily been derived from studies in mice, given the ethical restrictions and practical limitations of human embryos at the stage of PGC specification. However, recent studies have increasingly highlighted significant mechanistic differences for PGC development in humans and mice. The past decade has witnessed the establishment of human pluripotent stem cell (hPSC)-derived hPGC-like cells (hPGCLCs) as new models for studying hPGC fate specification and differentiation. In this review, we systematically summarize the current hPSC-derived models for hPGCLC induction, and how these studies uncover the regulatory machinery for human germ cell fate specification and differentiation, forming the basis for reconstituting gametogenesis in vitro from hPSCs for clinical applications and disease modeling.
早期胚胎发生过程中原始生殖细胞（PGC）的特化启动了生殖细胞谱系的发育，确保遗传和表观遗传信息从亲代传递给子代。生殖细胞发育缺陷可能导致不孕或出生缺陷。历史上，鉴于PGC特化阶段人类胚胎存在伦理限制和实际局限性，我们对人类PGC（hPGC）调控的理解主要源于对小鼠的研究。然而，最近的研究越来越多地强调人类和小鼠PGC发育在机制上存在显著差异。在过去十年中，人类多能干细胞（hPSC）衍生的hPGC样细胞（hPGCLC）已成为研究hPGC命运特化和分化的新模型。在这篇综述中，我们系统地总结了当前用于诱导hPGCLC的hPSC衍生模型，以及这些研究如何揭示人类生殖细胞命运特化和分化的调控机制，为从hPSC体外重建配子发生用于临床应用和疾病建模奠定基础。
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