2015年5月5日 讯 /生物谷BIOON/ --长期以来机体持续产生精子对于繁衍后代非常关键；近日，发表在国际杂志Development上的一篇研究论文中，来自日本国家基础生物学研究所的研究人员通过研究揭示了为何机体会持续产生精子，研究者Shosei Yoshida教授表示，精原干细胞对于类维生素A的反应存在一定的差异，而这种差异是机体精子持续产生的关键因子。
在哺乳动物睾丸中，精子在大部分雄性的一生时光中都会源源不断地产生，精原干细胞就是未成熟的生殖细胞，其会通过细胞分裂增加，同时会分化成为成熟的精子；为了能够持续产生精子，维持干细胞的数量和诱发向精子的分化之间的平衡非常关键。如果太多干细胞分化成为精子，那么精子发生将会最终被耗竭，而如果太多干细胞进行自我更新，睾丸就会充满未成熟的精子细胞。
在果蝇的睾丸中，其精原干细胞位于睾丸中的特殊微环境中，该环境名为“干细胞生境”，干细胞通常会被生境的功能所维持，一旦其离开微环境其就会分化成为精子，然而在哺乳动物的睾丸中尚没有发现可以维持精原干细胞的特殊干细胞生境，而且所发现的干细胞都被具有活性可以进行迁移，因此目前研究者并不清楚，哺乳动物的睾丸如何保持干细胞数量同诱导干细胞向精子分化过程之间的精细平衡。
文章中研究者发现精原干细胞依赖于不同的细胞亚型对类维生素A会产生反应性的差异，尽管所有的精原干细胞都会平等地“沐浴”在类维生素A中，但其会诱导一些但并不是所有的干细胞进行分化，随后研究者发现，精原干细胞对类维生素A的反应差异仅可以被其是否表达Rarγ基因所控制，Rarγ基因是一种类维生素A受体。
最后Yoshida教授说道，即使你收集到了成百上千只短期存活尺寸较小的果蝇，其绝对不会变成小鼠，而当小鼠和果蝇分享许多共性特征时，通过我们的研究就可以利用一种不同的策略来保护精子的发生，而如今我们观察到了多种生物存在的本源，而且清晰地阐明了雄性动物精子源源不断产生的根据，为研究生物有机体的繁殖提供了新的线索和思路。（生物谷Bioon.com）
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doi:10.1242/dev.118695
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Hierarchical differentiation competence in response to retinoic acid ensures stem cell maintenance during mouse spermatogenesis
Kanako Ikami1,2, Moe Tokue1,2,‡, Ryo Sugimoto1,*,‡, Chiyo Noda3, Satoru Kobayashi2,3, Kenshiro Hara1,2 and Shosei Yoshida1,2,§
Stem cells ensure tissue homeostasis through the production of differentiating and self-renewing progeny. In some tissues, this is achieved by the function of a definitive stem cell niche. However, the mechanisms that operate in mouse spermatogenesis are unknown because undifferentiated spermatogonia (Aundiff) are motile and intermingle with differentiating cells in an ‘open’ niche environment of seminiferous tubules. Aundiff include glial cell line-derived neurotrophic factor receptor α1 (GFRα1)+ and neurogenin 3 (NGN3)+ subpopulations, both of which retain the ability to self-renew. However, whereas GFRα1+ cells comprise the homeostatic stem cell pool, NGN3+ cells show a higher probability to differentiate into KIT+ spermatogonia by as yet unknown mechanisms. In the present study, by combining fate analysis of pulse-labeled cells and a model of vitamin A deficiency, we demonstrate that retinoic acid (RA), which may periodically increase in concentration in the tubules during the seminiferous epithelial cycle, induced only NGN3+ cells to differentiate. Comparison of gene expression revealed that retinoic acid receptor γ (Rarg) was predominantly expressed in NGN3+ cells, but not in GFRα1+ cells, whereas the expression levels of many other RA response-related genes were similar in the two populations. Ectopic expression of RARγ was sufficient to induce GFRα1+ cells to directly differentiate to KIT+ cells without transiting the NGN3+ state. Therefore, RARγ plays key roles in the differentiation competence of NGN3+ cells. We propose a novel mechanism of stem cell fate selection in an open niche environment whereby undifferentiated cells show heterogeneous competence to differentiate in response to ubiquitously distributed differentiation-inducing signals..
