Yu Danny C W, Wu Fang-Chun, Wu Chia-Eng, Chow Lu-Ping, Ho Hong-Nerng, Chen Hsin-Fu
Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University, Taipei, Taiwan.
Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan.
iScience. 2020 Dec 29;24(1):102003. doi: 10.1016/j.isci.2020.102003. eCollection 2021 Jan 22.
Understanding the mechanisms of human pluripotent stem cells (hPSCs) specification, development and differentiation to gametes are useful for elucidating the causes of infertility and potential treatment. This study aims to examine whether hPSCs can be induced to DDX4 extracellularly expressing primordial germ cell-like cells (DDX4 PGCLCs) and further into ovarian follicle stage in a combined and model. The transcriptional signatures show that these DDX4 PGCLCs are characteristic of PGCs and express ovarian folliculogenesis markers. We also verify that keratin (KRT)-8 is highly expressed in the DDX4 PGCLCs and plays a crucial role in germ cell migration. By co-culturing DDX4 PGCLCs with human granulosa cells (GCs), these cells are further induced into ovarian follicle-like structures in a xenograft mice model. This approach can in the future design practical strategies for treating germ cell-associated issues of infertility.
了解人类多能干细胞（hPSCs）向配子的特化、发育和分化机制，有助于阐明不孕症的病因及潜在治疗方法。本研究旨在探究在联合[具体内容未给出]模型中，hPSCs能否被诱导分化为细胞外表达DDX4的原始生殖细胞样细胞（DDX4 PGCLCs），并进一步发育至卵泡阶段。转录特征表明，这些DDX4 PGCLCs具有原始生殖细胞的特征，并表达卵泡发生标记物。我们还证实，角蛋白（KRT）-8在DDX4 PGCLCs中高表达，并在生殖细胞迁移中起关键作用。通过将DDX4 PGCLCs与人颗粒细胞（GCs）共培养，在异种移植小鼠模型中，这些细胞进一步被诱导形成卵泡样结构。这种方法未来可为治疗与生殖细胞相关的不孕症问题设计切实可行的策略。
