Hypermaintenance and hypofunction of aged spermatogonia: insight from age-related increase of Plzf expression.
Hypermaintenance and hypofunction of aged spermatogonia: insight from age-related increase of Plzf expression.
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DOI：
10.18632/oncotarget.4045
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发表时间：
2015-06-30
期刊：
影响因子：
--
通讯作者：
Wang N
中科院分区：
文献类型：
--
作者：
Ferder IC;Wang N
与其他组织中的干细胞一样，精原细胞，包括处于分化层次基础的精原干细胞（SSCs），也经历了与年龄相关的功能衰退。早幼粒细胞白血病锌指蛋白（Plzf）通过阻止精原细胞分化在维持精原细胞中起重要作用。为了评估Plzf表达是否存在与年龄相关的变化，我们发现老年小鼠睾丸表现出强大的“Plzf过表达”表型，因为它们不仅显示出更高频率的Plzf表达细胞，而且这些细胞中Plzf表达水平增加。此外，在老年睾丸中，一些Plzf表达细胞甚至异常地出现在分化中的精原细胞区室中，这些精原细胞区室通常是Plzf表达低或阴性的。重要的是，异位Plzf表达F9细胞抑制视黄酸（RA）诱导的Stra8激活，减数分裂启动所需的基因。这些数据，再加上我们的观察缺乏减数分裂启动精母细胞与高Plzf表达的精原细胞在老年睾丸，特别是在退化的曲细精管，表明年龄相关的增加Plzf表达的精原细胞老化的一种新的分子签名功能逮捕他们的分化。
Like stem cells in other tissues, spermatogonia, including spermatogonial stem cells (SSCs) at the foundation of differentiation hierarchy, undergo age-related decline in function. The promyelocytic leukemia zinc finger (Plzf) protein plays an essential role in spermatogonia maintenance by preventing their differentiation. To evaluate whether there is an age-related change in Plzf expression, we found that aged mouse testes exhibited a robust “Plzf overexpression” phenotype, in that they showed not only a higher frequency of Plzf-expressing cells but also an increased level of Plzf expression in these cells. Moreover, some Plzf-expressing cells in aged testes even aberrantly appeared in the differentiating spermatogonia compartment, which is usually low or negative for Plzf expression. Importantly, ectopic Plzf expression in F9 cells suppressed retinoic acid (RA)-induced Stra8 activation, a gene required for meiosis initiation. These data, together with our observation of a lack of meiosis-initiating spermatocytes associated with high Plzf-expressing spermatogonia in the aged testes, particularly in the degenerative seminiferous tubules, suggest that age-related increase in Plzf expression represents a novel molecular signature of spermatogonia aging by functionally arresting their differentiation.