Ecole Normale Supérieure de Lyon, Institut de Génomique Fonctionnelle de Lyon (IGFL), Université Lyon1, CNRS UMR 5242, INRA UMR1288, F-69364 Lyon, Cedex 07, France.
RNA. 2010 Apr;16(4):720-31. doi: 10.1261/rna.1963810. Epub 2010 Feb 11.
Spermatogenesis is a cyclic process in which diploid spermatogonia differentiate into haploid spermatozoa. This process is highly regulated, notably at the post-transcriptional level. MicroRNAs (miRNAs), single-stranded noncoding RNA molecules of about 20-25 nucleotides, are implicated in the regulation of many important biological pathways such as proliferation, apoptosis, and differentiation. We wondered whether miRNAs could play a role during spermatogenesis. The miRNA expression repertoire was tested in germ cells, and we present data showing that miR-34c was highly expressed only in these cells. Furthermore, our findings indicate that in male gonads, miR-34c expression is largely p53 independent in contrast to previous results showing a direct link in somatic cells between the miR-34 family and this tumor suppressor protein. In order to identify target genes involved in germinal lineage differentiation, we overexpressed miR-34c in HeLa cells, analyzed the transcriptome of these modified cells, and noticed a shift of the expression profile toward the germinal lineage. Recently, it has been shown that exogenous expression of Ddx4/Vasa in embryonic chicken stem cells (cESC) induces cESC reprogramming toward a germ cell fate. When we simultaneously expressed miR-34c in such cells, we could detect an up-regulation of germ cell-specific genes whereas the expression of other lineage specific markers remained unchanged. These data suggest that miR-34c could play a role by enhancing the germinal phenotype of cells already committed to this lineage.
精子发生是一个周期过程,其中二倍体精原细胞分化为单倍体精子。这个过程受到高度调控,尤其是在转录后水平。microRNAs(miRNAs)是约 20-25 个核苷酸的单链非编码 RNA 分子,参与许多重要生物学途径的调节,如增殖、凋亡和分化。我们想知道 miRNAs 是否在精子发生过程中发挥作用。我们在生殖细胞中测试了 miRNA 的表达谱,结果表明 miR-34c 仅在这些细胞中高度表达。此外,我们的研究结果表明,在雄性性腺中,miR-34c 的表达在很大程度上与 p53 无关,与之前在体细胞中显示 miR-34 家族与该肿瘤抑制蛋白之间存在直接联系的结果形成对比。为了鉴定参与生殖细胞谱系分化的靶基因,我们在 HeLa 细胞中转染 miR-34c,分析这些修饰细胞的转录组,注意到表达谱向生殖细胞谱系的转变。最近,已经表明在胚胎鸡干细胞(cESC)中外源表达 Ddx4/Vasa 可诱导 cESC 向生殖细胞命运重编程。当我们在这些细胞中同时表达 miR-34c 时,我们可以检测到生殖细胞特异性基因的上调,而其他谱系特异性标记物的表达保持不变。这些数据表明,miR-34c 可以通过增强已经向该谱系定向的细胞的生殖表型来发挥作用。