Rodríguez Gutiérrez Daniel, Eid Wassim, Biason-Lauber Anna
Section of Medicine, Endocrinology Division, University of Fribourg, Fribourg, Switzerland.
Department of Biochemistry, Medical Research Institute, University of Alexandria, Alexandria, Egypt.
Front Genet. 2018 Oct 24;9:498. doi: 10.3389/fgene.2018.00498. eCollection 2018.
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 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.
支持细胞是男性性腺发育的主要参与者，对它们的研究可能有助于揭示46,XY性发育障碍（DSD）。成熟的原代支持细胞在长期培养中无法增殖，现有的支持细胞模型存在一些局限性，因为它们来源于小鼠或人类癌症组织。我们将人类成纤维细胞（HFs）来源的诱导多能干细胞分化为支持样细胞（SLC），为了表征这个新的支持细胞模型，我们通过下一代测序技术进行了基因表达分析。这种方法表明，我们假定的SLC多能性标志物表达降低，并表达支持细胞标志物，如SRY相关高迁移率族蛋白盒9（SOX9）、波形蛋白（VIM）和紧密连接蛋白11（CLDN-11）。更详细地说，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能力，我们能够生成与人类支持细胞（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佳来源，这对于性发育和生殖医学的基础研究和个性化医疗可能具有至关重要的意义。
