Wu Changqing, Xu Bo, Li Xiaoyong, Ma Wenzhi, Zhang Ping, Chen Xuejin, Wu Ji
Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai 200240, China.
Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan 750004, China.
Mol Ther. 2017 Jun 7;25(6):1408-1419. doi: 10.1016/j.ymthe.2017.04.019. Epub 2017 May 18.
It has long been believed that most female mammalian species lose the ability to generate oocytes in postnatal ovaries. Recent evidence has demonstrated the isolation and culture of female germline stem cells (FGSCs) from adult mice and humans. However, the process and mechanisms of FGSC differentiation in vivo following transplantation have not yet been studied. Here, we isolated and characterized FGSCs from a single EGFP-transgenic mouse, and traced the development and behavior of transplanted FGSCs (F-TFs) in vivo. Comparisons of folliculogenesis between recipients with FGSC transplantation and wild-type (WT) mice were performed by single follicle RNA-sequencing (RNA-seq). Results showed that FGSCs exhibited a homing ability and began to differentiate into early-stage oocytes only when they reached the edge of the ovarian cortex. The F-TFs restored function of premature ovarian failure (gdf9iCre; Pten genotype) and generated offspring. Furthermore, results demonstrated that the developmental mechanisms of follicles derived from F-TFs were similar to that of WT follicles. Weighted gene co-expression network analysis identified two potential sub-networks and core genes that played a critical role in follicular development. These findings provide a theoretical basis and lay a technology platform for specific or personalized medical treatment of ovarian failure or other ovarian diseases.
长期以来，人们一直认为大多数雌性哺乳动物在出生后的卵巢中失去了产生卵母细胞的能力。最近的证据表明，已从成年小鼠和人类中分离并培养出了雌性生殖系干细胞（FGSCs）。然而，移植后FGSCs在体内的分化过程和机制尚未得到研究。在此，我们从一只EGFP转基因小鼠中分离并鉴定了FGSCs，并在体内追踪了移植的FGSCs（F-TFs）的发育和行为。通过单卵泡RNA测序（RNA-seq）对接受FGSC移植的受体与野生型（WT）小鼠之间的卵泡发生进行了比较。结果表明，FGSCs具有归巢能力，并且只有当它们到达卵巢皮质边缘时才开始分化为早期卵母细胞。F-TFs恢复了卵巢早衰（gdf9iCre；Pten基因型）的功能并产生了后代。此外，结果表明源自F-TFs的卵泡的发育机制与WT卵泡相似。加权基因共表达网络分析确定了两个潜在的子网和在卵泡发育中起关键作用的核心基因。这些发现为卵巢衰竭或其他卵巢疾病的特异性或个性化医学治疗提供了理论基础并奠定了技术平台。
