Tracing and Characterizing the Development of Transplanted Female Germline Stem Cells In Vivo
Tracing and Characterizing the Development of Transplanted Female Germline Stem Cells In Vivo
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追踪和表征移植的雌性生殖干细胞在体内的发育
DOI：
10.1016/j.ymthe.2017.04.019
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发表时间：
2017-06-07
影响因子：
12.4
通讯作者：
Wu, Ji
中科院分区：
文献类型：
--
作者：
Wu, Changqing;Xu, Bo;Wu, Ji
长期以来，人们一直认为大多数雌性哺乳动物物种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，从成年小鼠和人类中分离和培养雌性生殖系干细胞（FGSC）。然而，移植后FGSC在体内分化的过程和机制尚未研究。在这里，我们从单个EGFP转基因小鼠中分离和表征FGSC，并追踪移植的FGSC（F-TF）在体内的发育和行为。通过单卵泡RNA测序（RNA-seq）比较FGSC移植受体和野生型（WT）小鼠之间的卵泡发生。结果表明，FGSCs具有归巢能力，当到达卵巢皮质边缘时，FGSCs开始分化为早期卵母细胞。F-TF恢复了卵巢早衰（gdf 9 iCre; Pten（lox/loxp）基因型）的功能并产生后代。此外，结果表明，F-TF衍生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络和核心基因，在卵泡发育中发挥了关键作用。这些发现为卵巢功能衰竭或其他卵巢疾病的特异性或个性化药物治疗提供了理论依据和技术平台。
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(lox/loxp) 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.