Zovoilis Athanasios, Nolte Jessica, Drusenheimer Nadja, Zechner Ulrich, Hada Hiroki, Guan Kaomei, Hasenfuss Gerd, Nayernia Karim, Engel Wolfgang
Institute of Human Genetics, University of Goettingen, Heinrich-Dueker- Weg 12, Goettingen D-37073, Germany.
Mol Hum Reprod. 2008 Sep;14(9):521-9. doi: 10.1093/molehr/gan044. Epub 2008 Aug 12.
Spermatogonial stem cells (SSCs) isolated from the adult mouse testis and cultured have been shown to respond to culture conditions and become pluripotent, so called multipotent adult germline stem cells (maGSCs). microRNAs (miRNAs) belonging to the 290 and 302 miRNA clusters have been previously classified as embryonic stem cell (ESC) specific. Here, we show that these miRNAs generally characterize pluripotent cells. They are expressed not only in ESCs but also in maGSCs as well as in the F9 embryonic carcinoma cell (ECC) line. In addition, we tested the time-dependent influence of different factors that promote loss of pluripotency on levels of these miRNAs in all three pluripotent cell types. Despite the differences regarding time and extent of differentiation observed between ESCs and maGSCs, expression profiles of both miRNA families showed similarities between these two cell types, suggesting similar underlying mechanisms in maintenance of pluripotency and differentiation. Our results indicate that the 290-miRNA family is connected with Oct-4 and maintenance of the pluripotent state. In contrast, members of the 302-miRNA family are induced during first stages of in vitro differentiation in all cell types tested. Therefore, detection of miRNAs of miR-302 family in pluripotent cells can be attributed to the proportion of spontaneously differentiating cells in cultures of pluripotent cells. These results are consistent with ESC-like nature of maGSCs and their potential as an alternative source of pluripotent cells from non-embryonic tissues.
从成年小鼠睾丸分离并培养的精原干细胞（SSCs）已被证明会对培养条件作出反应并成为多能性细胞，即所谓的多能成年生殖系干细胞（maGSCs）。属于290和302 miRNA簇的微小RNA（miRNA）先前已被归类为胚胎干细胞（ESC）特异性的。在此，我们表明这些miRNA通常是多能性细胞的特征。它们不仅在ESC中表达，也在maGSCs以及F9胚胎癌细胞（ECC）系中表达。此外，我们测试了不同促进多能性丧失的因子对所有三种多能性细胞类型中这些miRNA水平的时间依赖性影响。尽管在ESC和maGSCs之间观察到了分化时间和程度上的差异，但这两个miRNA家族的表达谱在这两种细胞类型之间显示出相似性，表明在维持多能性和分化方面存在相似的潜在机制。我们的结果表明，290-miRNA家族与Oct-4以及多能性状态的维持相关。相反，302-miRNA家族的成员在所有测试细胞类型的体外分化第一阶段被诱导。因此，在多能性细胞中检测到miR-302家族的miRNA可归因于多能性细胞培养物中自发分化细胞的比例。这些结果与maGSCs的ESC样性质及其作为来自非胚胎组织的多能性细胞替代来源的潜力一致。
