Song Hye-Won, Wilkinson Miles F
Department of Reproductive Medicine, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Department of Reproductive Medicine, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Semin Cell Dev Biol. 2014 Jun;30:14-26. doi: 10.1016/j.semcdb.2014.02.005. Epub 2014 Feb 19.
Spermatogenesis is a multistep process that generates millions of spermatozoa per day in mammals. A key to this process is the spermatogonial stem cell (SSC), which has the dual property of continually renewing and undergoing differentiation into a spermatogonial progenitor that expands and further differentiates. In this review, we will focus on how these proliferative and early differentiation steps in mammalian male germ cells are controlled by transcription factors. Most of the transcription factors that have so far been identified as promoting SSC self-renewal (BCL6B, BRACHYURY, ETV5, ID4, LHX1, and POU3F1) are upregulated by glial cell line-derived neurotrophic factor (GDNF). Since GDNF is crucial for promoting SSC self-renewal, this suggests that these transcription factors are responsible for coordinating the action of GDNF in SSCs. Other transcription factors that promote SSC self-renewal are expressed independently of GDNF (FOXO1, PLZF, POU5F1, and TAF4B) and thus may act in non-GDNF pathways to promote SSC cell growth or survival. Several transcription factors have been identified that promote spermatogonial differentiation (DMRT1, NGN3, SOHLH1, SOHLH2, SOX3, and STAT3); some of these may influence the decision of an SSC to commit to differentiate while others may promote later spermatogonial differentiation steps. Many of these transcription factors regulate each other and act on common targets, suggesting they integrate to form complex transcriptional networks in self-renewing and differentiating spermatogonia.
精子发生是一个多步骤过程，在哺乳动物中每天能产生数百万个精子。这一过程的关键是精原干细胞（SSC），它具有持续自我更新和分化为精原祖细胞的双重特性，精原祖细胞会进一步增殖并分化。在本综述中，我们将聚焦于哺乳动物雄性生殖细胞的这些增殖和早期分化步骤是如何由转录因子控制的。目前已确定的大多数促进SSC自我更新的转录因子（BCL6B、短尾、ETV5、ID4、LHX1和POU3F1）都由胶质细胞系衍生的神经营养因子（GDNF）上调。由于GDNF对促进SSC自我更新至关重要，这表明这些转录因子负责协调GDNF在SSC中的作用。其他促进SSC自我更新的转录因子独立于GDNF表达（FOXO1、PLZF、POU5F1和TAF4B），因此可能通过非GDNF途径促进SSC细胞生长或存活。已确定了几种促进精原细胞分化的转录因子（DMRT1、NGN3、SOHLH1、SOHLH2、SOX3和STAT3）；其中一些可能影响SSC决定进行分化，而其他一些可能促进后期精原细胞分化步骤。这些转录因子中的许多相互调节并作用于共同靶点，表明它们整合形成复杂的转录网络，参与精原细胞的自我更新和分化。
