EWSR1 is critical for post-meiotic transcription and spermiogenesis

Spermatogenesis is precisely controlled by complex gene expression programs. During mammalian male germ cell development, a crucial feature is the repression of transcription before spermatid elongation. Previously, we discovered that RNA-binding protein EWSR1 plays an important role in meiotic recombination and is highly expressed in late meiotic cells and post-meiotic cells. Here, we used a Ewsr1 pachytene stage-specific knockout mouse model to study its roles at late meiotic prophase I and in spermatozoa maturation. We show that loss of EWSR1 at this stage does not affect proper meiosis completion, but the developing germ cells exhibit defects in spermatid elongation and chromocenter formation. In the Ewsr1 conditional knockout testes, expression of many genes regulating spermatid differentiation is impaired, suggesting that EWSR1 may play important role in regulation of spermiogenesis related mRNA synthesis and spermatid differentiation. RNA-seq of spermatocytes and round spermatids isolated by FACS sorting from Ewsr1 control and conditional knockout mice

精子发生（spermatogenesis）受复杂的基因表达程序精准调控。在哺乳动物雄性生殖细胞发育进程中，精子细胞伸长前的转录抑制是一项核心特征。本团队此前发现，RNA结合蛋白（RNA-binding protein）EWSR1在减数分裂重组中发挥关键作用，且在减数分裂后期细胞及减数分裂后细胞中呈高表达状态。本研究构建并利用Ewsr1粗线期特异性基因敲除小鼠模型，探究其在减数分裂I前期晚期及精子成熟过程中的功能。研究结果显示，该阶段EWSR1的缺失不会影响减数分裂的正常完成，但发育中的生殖细胞会出现精子细胞伸长异常及染色中心（chromocenter）形成缺陷。在Ewsr1条件性敲除小鼠的睾丸组织中，诸多调控精子细胞分化的基因表达受到损伤，这提示EWSR1可能在精子形成（spermiogenesis）相关mRNA合成及精子细胞分化的调控中发挥重要作用。本研究对从Ewsr1野生型对照及条件性敲除小鼠中通过FACS分选分离得到的精母细胞与圆形精子细胞开展了RNA测序。