Vaccinia-related kinase 1 is required for the maintenance of undifferentiated spermatogonia in mouse male germ cells.
Vaccinia-related kinase 1 is required for the maintenance of undifferentiated spermatogonia in mouse male germ cells.
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DOI：
10.1371/journal.pone.0015254
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发表时间：
2010-12-13
期刊：
影响因子：
3.7
通讯作者：
Kim KT
中科院分区：
文献类型：
--
作者：
Choi YH;Park CH;Kim W;Ling H;Kang A;Chang MW;Im SK;Jeong HW;Kong YY;Kim KT
牛痘相关激酶1（VRK 1）是一种重要的有丝分裂调控蛋白激酶。已知VRK 1在生殖细胞发育中起作用，其缺陷导致不育。在这里，我们描述了VRK 1是必不可少的精原干细胞的维护。为了确定VRK 1是否在这些细胞中发挥作用，我们评估了未分化精原细胞的群体大小。流式细胞仪分析表明，未分化的精原细胞的数量显着减少VRK 1缺陷的睾丸。VRK 1在精原细胞群体中高度表达，大约66%的未分化精原细胞被分选为Ep-CAM+/c-kit−/α-6-integrin+群体，显示VRK 1阳性信号。表达Plzf和Oct 4但不表达c-kit的未分化干细胞也表达VRK 1，表明VRK 1是维持精原干细胞的内在因子。微阵列分析的全球睾丸转录组和定量RT-PCR VRK 1缺陷的睾丸显示显着降低未分化精原标记基因在出生后早期小鼠的表达水平。总之，这些结果表明，VRK 1是所需的未分化的精原细胞的增殖和分化，这是必要的生精细胞的维持。
Vaccinia-related kinase 1 (VRK1) is a crucial protein kinase for mitotic regulation. VRK1 is known to play a role in germ cell development, and its deficiency results in sterility. Here we describe that VRK1 is essential for the maintenance of spermatogonial stem cells. To determine whether VRK1 plays a role in these cells, we assessed the population size of undifferentiated spermatogonia. Flow cytometry analyses showed that the number of undifferentiated spermatogonia was markedly reduced in VRK1-deficient testes. VRK1 was highly expressed in spermatogonial populations, and approximately 66% of undifferentiated spermatogonia that were sorted as an Ep-CAM+/c-kit−/alpha-6-integrin+ population showed a positive signal for VRK1. Undifferentiated stem cells expressing Plzf and Oct4 but not c-kit also expressed VRK1, suggesting that VRK1 is an intrinsic factor for the maintenance of spermatogonial stem cells. Microarray analyses of the global testicular transcriptome and quantitative RT-PCR of VRK1-deficient testes revealed significantly reduced expression levels of undifferentiated spermatogonial marker genes in early postnatal mice. Together, these results suggest that VRK1 is required for the proliferation and differentiation of undifferentiated spermatogonia, which are essential for spermatogenic cell maintenance.
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