3月10日，国际学术期刊Development 在线发表了中国科学院上海生命科学研究院生物化学与细胞生物学研究所童明汉研究组的最新研究成果：Retinoid signaling controls spermatogonial differentiation by regulating expression of replication-dependent core histone genes。
精子发生（spermatogenesis）是一个起始于精原干细胞，完成于长形精子的高度复杂和特化的细胞发育过程。精原细胞分化是精子发生的关键步骤，也是精子发生不可逆转的起始。维生素A的活性代谢产物维甲酸(retinoic acid, RA)在精原细胞分化过程中发挥关键调控作用，但其具体调控机制并不清楚。
童明汉研究组的博士研究生陈瑶应用特异性失活生殖细胞或支持细胞内维甲酸信号系统的小鼠模型，发现维甲酸能促进未分化精原细胞进入细胞周期S期，通过精原细胞自身直接调控精原细胞分化。进一步的研究表明，维甲酸信号通路通过控制包括Hist1 cluster在内的靶基因的表达调控精原细胞分化。
该工作在研究员童明汉的指导下完成，参与该研究的包括美国华盛顿州立大学的Michael D. Griswold实验室和中科院上海生科院计算生物学研究所魏刚研究组。该工作得到生化与细胞所细胞分析技术平台、分子生物学技术平台的支持与帮助，受到国家科技部、国家自然科学基金委以及上海生科院的经费支持。
维甲酸调控精原细胞分化分子机制模式图
原文摘要：
Retinoid signaling controls spermatogonial differentiation by regulating expression of replication-dependent core histone genes
Retinoic acid (RA) signaling is critical for spermatogonial differentiation, which is a key step for spermatogenesis. We explored the mechanisms underlying spermatogonial differentiation by targeting expression of a dominant-negative mutant of RA receptor α (RARα) specifically to the germ cells of transgenic mice to subvert the activity of endogenous receptors. Here we show that (i) inhibition of retinoid signaling in germ cells completely blocked spermatogonial differentiation identical to vitamin A-deficient (VAD) mice; (ii) the blockage of spermatogonial differentiation by impaired retinoid signaling resulted from an arrest of entry of the undifferentiated spermatogonia into S phase; and (iii) retinoid signaling regulated spermatogonial differentiation through controlling expression of its direct target genes including replication-dependent core histone genes. Altogether, our results demonstrate that the action of retinoid signaling on spermatogonial differentiation in vivo is direct through spermatogonia self, and provide the first evidence that this is mediated by regulation of expression of replication-dependent core histone genes.