Ding Xinbao, Liu Guishu, Xu Bo, Wu Changqing, Hui Ning, Ni Xin, Wang Jian, Du Meirong, Teng Xiaoming, Wu Ji
Renji Hospital Shanghai Jiaotong University School of Medicine, Key Laboratory for the Genetics of Developmental &Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai 200240, China.
The First People's Hospital of Chenzhou, Chenzhou 42300, Hunan, China.
Sci Rep. 2016 Jun 30;6:28218. doi: 10.1038/srep28218.
Human female germline stem cells (FGSCs) have opened new opportunities for understanding human oogenesis, delaying menopause, treating infertility, and providing a new strategy for preserving fertility. However, the shortage of adult human ovaries tissues available impedes their future investigations and clinical applications. Here, we have established FGSC lines from scarce ovarian cortical tissues that exist in follicular aspirates (faFGSCs), which are produced and discarded in in vitro fertilization centers worldwide. The faFGSCs have characteristics of germline stem cells involved in the gene expression profile, growth characteristics, and a normal karyotype consistent with that of FGSCs obtained from ovarian cortexes surgically removed from patients (srFGSCs). Furthermore, faFGSCs have developmental potentials including spontaneous differentiation into oocytes under feeder-free conditions, communicating with granulosa cells by gap junctions and paracrine factors, entering meiosis after RA induction, as well as forming follicles after injection into human ovarian cortical tissues xenografted into adult immunodeficient female mice. Lastly, we developed a strategy guiding FGSCs differentiated into germinal vesicle (GV) stage oocytes in vitro and revealed their developmental mechanisms. Our study not only provides a new approach to obtain human FGSCs for medical treatment, but also opens several avenues to investigate human oogenesis in vitro.
人类雌性生殖系干细胞（FGSCs）为理解人类卵子发生、延缓绝经、治疗不孕症以及提供一种新的生育力保存策略带来了新机遇。然而，可用的成人人类卵巢组织短缺阻碍了对其进一步的研究和临床应用。在此，我们从卵泡抽吸物中存在的稀少卵巢皮质组织中建立了FGSC系（faFGSCs），这些卵泡抽吸物在全球体外受精中心产生并被丢弃。faFGSCs具有生殖系干细胞的特征，涉及基因表达谱、生长特性以及与从手术切除患者卵巢皮质获得的FGSCs（srFGSCs）一致的正常核型。此外，faFGSCs具有发育潜能，包括在无饲养层条件下自发分化为卵母细胞、通过缝隙连接和旁分泌因子与颗粒细胞通讯、在视黄酸诱导后进入减数分裂，以及在注射到移植到成年免疫缺陷雌性小鼠体内的人类卵巢皮质组织后形成卵泡。最后，我们开发了一种策略，指导FGSCs在体外分化为生发泡（GV）期卵母细胞并揭示其发育机制。我们的研究不仅为获得用于医学治疗的人类FGSCs提供了一种新方法，还为体外研究人类卵子发生开辟了多条途径。
