Expression profile of male germ cell-associated genes in mouse embryonic stem cell cultures treated with all-trans retinoic acid and testosterone.
Expression profile of male germ cell-associated genes in mouse embryonic stem cell cultures treated with all-trans retinoic acid and testosterone.
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DOI：
10.1002/mrd.20925
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发表时间：
2009-01
影响因子：
2.5
通讯作者：
Strauss, Jerome F., III
中科院分区：
文献类型：
--
作者：
Silva, Celso;Wood, Jennifer R.;Salvador, Lisa;Zhang, Zhibing;Kostetskii, Igor;Williams, Carmen J.;Strauss, Jerome F., III
在形态和功能上类似于雄性生殖细胞的细胞可以自发地来源于ES细胞。然而，这一过程是低效的和不可预测的，表明在自发ES细胞分化过程中雄性生殖细胞相关基因的表达模式不能模拟基因的体内谱。因此，在本研究中，在雄性生殖细胞发育的不同阶段表达的基因的时间表达谱在分化的ES细胞进行了检查。全反式维甲酸（RA），这是一个已知的诱导剂的原始生殖细胞（PGC）的增殖/存活在体外和睾酮，这是所需的精子发生在体内对这些基因的表达的影响也被确定。分析的12个基因中的每一个在未处理的分化ES细胞中表现出四种时间表达模式之一：逐渐降低（Dpp 3a，Sycp 3，Msy 2），最初低然后增加（Stra 8，Sycp 1，Dazl，Act，Prm 1），最初降低然后增加（Piwil 2，Tex 14），或相对不变（Akap 3，Odf 2）。与未处理的对照组相比，RA处理的细胞显示Stra 8、Dazl、Act和Prm 1的表达增加，并抑制Dpp 3a的表达。此外，睾酮增加Stra 8的表达，而RA和睾酮的组合协同增加Act的表达。我们的研究结果建立了一个全面的男性生殖细胞的基因表达在自发分化的小鼠ES细胞和描述的能力，RA和睾酮调节这些基因的表达。此外，这些数据代表了设计合理的雄性生殖细胞定向分化方案的重要的第一步。
Cells that morphologically and functionally resemble male germ cells can be spontaneously derived from ES cells. However, this process is inefficient and unpredictable suggesting that the expression pattern of male germ cell associated genes during spontaneous ES cell differentiation does not mimic the in vivo profiles of the genes. Thus, in the present study, the temporal expression profile of genes expressed at different stages of male germ cell development was examined in differentiating ES cells. The effect of all-trans retinoic acid (RA) which is a known inducer of primordial germ cell (PGC) proliferation/survival in vitro and testosterone which is required for spermatogenesis in vivo on the expression of these genes was also determined. Each of the 12 genes analyzed exhibited one of four temporal expression patterns in untreated differentiating ES cells: progressively decreased (Dpp3a, Sycp3, Msy2), initially low and then increased (Stra8, Sycp1, Dazl, Act, Prm1), initially decreased and then increased (Piwil2, Tex14), or relatively unchanged (Akap3, Odf2). RA-treated cells exhibited increased expression of Stra8, Dazl, Act, and Prm1 and suppressed expression of Dpp3a compared to untreated controls. Furthermore, testosterone increased expression of Stra8 while the combination of RA and testosterone synergistically increased expression of Act. Our findings establish a comprehensive profile of male germ cell gene expression during spontaneous differentiation of murine ES cells and describe the capacity of RA and testosterone to modulate the expression of these genes. Furthermore, these data represent an important first step in designing a plausible directed differentiation protocol for male germ cells.
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