Isolation of genes involved in carcinogenesis of spermat ogonial stem cells

生精是由生精小管中的生殖细胞和体细胞相互作用启动的。我们试图鉴定在只含有A型精原生殖细胞和支持细胞的JSD/JSD突变小鼠睾丸中特异表达的基因，而不是在W/WV试验中存在支持细胞和少数生殖细胞的地方。利用基因芯片和代表性差异分析，我们分离了20个已知基因和4个新基因。代表有Lipocalin家族成员的基因(前列腺素D合成酶和24p3)和肿瘤抑制基因(蛋白磷酸酶TD14和Sui1)。所有这些JSD/JSD衍生的24个基因不仅在JSD/JSD试验IS中高表达，而且在隐睾性IS中也高表达，这表明选择性基因的表达不是由一个尚未鉴定的JSD基因产物直接引起的，而是与精原细胞分化的停止有关。原位杂交、流式细胞仪鉴定和逆转录聚合酶链式反应分析表明，这些基因在发育中的性腺和成年睾丸的精原生殖细胞和体细胞中均有表达。由于这些JSD/JSD衍生基因的mRNAs在W/WV睾丸中几乎检测不到，我们认为一组睾丸基因的表达受早期精原生殖细胞的存在调控。

Spermatogensis is initiated by the interaction of germ cells and somatic cells in the seminiferous tubules. We attempted to identify genes which are specifically expressed in jsd/jsd mutant mouse testis containing only type A spermatogonial germ cells and Sertoli cells, but not in W/Wv test is where Sertoli cells and few germ cells are present. By taking advantage of cDNA microarrays and representational difference analysis, we isolated 20 known genes and 4 novel genes. Representatives are genes for lipocalin family members (prostaglandin D synthetase and 24p3) and tumor suppressors (protein phosphatase TD14 and Sui1). All of these jsd/jsd derived 24 genes were highly expressed not only in jsd/jsd test is but also in cryptorchid test is, indicating that the selective gene expression is not directly caused by a yet uncharacterized jsd gene product, but rather correlated with cessation of spermatogonial differentiation. In situ hybridization analyses and flow cytometric sorting followed by reverse transcriptase-PCRrevealed that these genes are expressed in both spermatogonial germ cells and somatic cells in developing gonad and adult testis. As mRNAs of these jsd/jsd-derived genes were barely detectable in W/Wv testis, we proposethat expression of a group of testicular genes are regulated by the presence of early spermatogonial germ cells.