Retinoic acid metabolism links the periodical differentiation of germ cells with the cycle of Sertoli cells in mouse seminiferous epithelium
Retinoic acid metabolism links the periodical differentiation of germ cells with the cycle of Sertoli cells in mouse seminiferous epithelium
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DOI：
10.1016/j.mod.2011.12.003
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发表时间：
2012-01-01
影响因子：
2.6
通讯作者：
Yoshida, Shosei
中科院分区：
文献类型：
--
作者：
Sugimoto, Ryo;Nabeshima, Yo-ichi;Yoshida, Shosei
组织的稳态依赖于干细胞分化的调节。在小鼠生精小管的上皮中，具有干细胞功能的未分化精原细胞（A(undiff)）向精子的分化过程以周期性方式发生，称为“生精上皮周期”。为了确定这种周期性分化的机制，我们研究了支持细胞（体细胞支持细胞）和视黄酸（RA）在生精上皮周期中的作用。支持细胞以与生殖细胞分化协调的方式周期性地改变其功能，并支持精子发生的整个过程。已知 RA 在这种周期性分化中发挥重要作用，但其精确的作用模式和调节仍然很大程度上不清楚。我们表明，实验性增加 RA 信号传导既能够诱导 A（无差异）分化，又能将支持细胞周期重置到适当的阶段。然而，外源 RA 信号对 A(undiff) 和支持细胞的这些作用受到密切位置的分化生殖细胞的强烈干扰。基于RA代谢相关基因在多种细胞类型（包括生殖细胞和支持细胞）中的表达及其通过RA信号传导的调节，我们在此提出分化的生殖细胞在调节局部RA代谢中发挥主要作用，从而导致A（undiff）的定时分化和支持细胞的适当循环。通过调节局部环境来分化后代的类似调节也可能涉及其他干细胞系统。 (C) 2011 Elsevier Ireland Ltd. 保留所有权利。
Homeostasis of tissues relies on the regulated differentiation of stem cells. In the epithelium of mouse seminiferous tubules, the differentiation process from undifferentiated spermatogonia (A(undiff)), which harbor the stem cell functions, to sperm occurs in a periodical manner, known as the "seminiferous epithelial cycle". To identify the mechanism underlying this periodic differentiation, we investigated the roles of Sertoli cells (the somatic supporting cells) and retinoic acid (RA) in the seminiferous epithelial cycle. Sertoli cells cyclically change their functions in a coordinated manner with germ cell differentiation and support the entire process of spermatogenesis. RA is known to play essential roles in this periodic differentiation, but its precise mode of action and its regulation remains largely obscure. We showed that an experimental increase in RA signaling was capable of both inducing A(undiff) differentiation and resetting the Sertoli cell cycle to the appropriate stage. However, these actions of exogenous RA signaling on A(undiff) and Sertoli cells were strongly interfered by the differentiating germ cells of intimate location. Based on the expression of RA metabolism-related genes among multiple cell types - including germ and Sertoli cells - and their regulation by RA signaling, we propose here that differentiating germ cells play a primary role in modulating the local RA metabolism, which results in the timed differentiation of A(undiff) and the appropriate cycling of Sertoli cells. Similar regulation by differentiating progeny through the modulation of local environment could also be involved in other stem cell systems. (C) 2011 Elsevier Ireland Ltd. All rights reserved.