A Human Gonadal Cell Model From Induced Pluripotent Stem Cells.
A Human Gonadal Cell Model From Induced Pluripotent Stem Cells.
复制标题
DOI：
10.3389/fgene.2018.00498
复制
发表时间：
2018
影响因子：
3.7
通讯作者：
Biason-Lauber A
中科院分区：
文献类型：
--
作者：
Rodríguez Gutiérrez D;Eid W;Biason-Lauber A
支持细胞是男性性腺发育的主要参与者，对支持细胞的研究有助于阐明46，XY性发育障碍（DSD）的发病机制。成熟的原代Sertoli细胞不能在长期的体外培养中增殖，并且可用的Sertoli细胞模型具有若干限制，因为它们源自小鼠或人癌组织。我们将人成纤维细胞（HF）衍生的诱导多能干细胞分化为支持样细胞（SLC），为了表征这种新的支持细胞模型，我们通过下一代测序技术进行了基因表达分析。这种方法揭示了我们推定的SLC具有降低的多能性标志物表达和表达的支持细胞标志物，如SRY相关的HMG-盒9（SOX 9）、波形蛋白（Vim）和密蛋白-11（CLDN-11）。更详细地，转录谱分析表明，这些细胞处于支持细胞成熟的早期阶段。利用诱导多能干细胞的力量，我们能够产生与人类支持细胞（HSerCs）具有遗传和功能相似性的SLC。SLC可能成为患者特异性支持细胞的极好来源，这可能对性发育和生殖医学的基础研究和个性化医学都有极大的益处。
Sertoli cells are main players in the male gonads development and their study may shed light on 46,XY disorders of sex development (DSD). Mature primary Sertoli cells are incapable of proliferating in prolonged in vitro cultures and the available Sertoli cell models have several limitations since they derive from mouse or human cancer tissues. We differentiated human fibroblasts (HFs)-derived induced pluripotent stem cells into Sertoli-like cells (SLC) and, in order to characterize this new Sertoli cell model, we performed gene expression analyses by NextGeneration Sequencing techniques. This approach revealed that our putative SLC have reduced expression of pluripotency markers and expressed Sertoli cell markers such as SRY-Related HMG-Box 9 (SOX9), vimentin (VIM), and claudin-11 (CLDN-11). More in detail, the transcriptional profile analysis suggested that these cells are in an early stage of Sertoli cells maturation. Harnessing the power of induced pluripotent stem cells, we were able to generate SLC that show genetic and functional similarities to human Sertoli cells (HSerCs). SLC could become an excellent source of patient-specific Sertoli cells that could be of paramount benefit for both basic research and personalized medicine in sex development and reproductive medicine.