Transcriptome analysis of the responses to methyl methanesulfonate treatment in mouse pachytene spermatocytes and round spermatids
Transcriptome analysis of the responses to methyl methanesulfonate treatment in mouse pachytene spermatocytes and round spermatids
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小鼠粗线期精母细胞和圆形精子细胞对甲磺酸甲酯处理反应的转录组分析
DOI：
10.1016/j.gene.2016.10.006
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发表时间：
2016
期刊：
影响因子：
3.5
通讯作者：
Guo Caixia
中科院分区：
文献类型：
--
作者：
Zhang Hui;Zhang Chuanchao;Yan Jinting;Sun Zhongshuai;Song Shuhui;Sun Yazhou;Guo Caixia
DNA烷基化剂是一类主要的DNA损伤剂，它对精子发生造成威胁。目前，关于小鼠生精细胞转录组谱在精子发生的不同阶段对DNA烷基化反应的改变知之甚少。在这项研究中，在甲基磺酸盐（MMS）处理后0或30分钟，以及未处理的对照组，对粗线精母细胞（PS）和圆形精母细胞（RS）进行RNA测序（RNA-seq）。通过比较三组分别在PS和RS中鉴定出大量差异表达基因（DEGs）。所有deg的功能分析强调了蛋白质泛素化途径和DNA损伤反应（DDR）网络是两种细胞类型中共同的两个主要生物学过程。进一步分析在修复30分钟内与对照组相比发生2倍或更多变化的deg，表明RS中PS和DDR相关通路中几个细胞因子信号通路分别受到最强烈的影响。基因本体（GO）分析直接显示了PS和RS之间的差异生物过程（BP），其中PS中“转录调控”和RS中“细胞应激反应”分别被过度代表。此外，在所有DEGs中，筛选和聚类了374个PS和158个RS中的ddr相关基因，显示了PS和RS中ddr相关基因的动态表达模式。
Spermatogenesis is threatened by DNA alkylating agents, one major category of DNA damaging agents. Currently, little is known about the alterations in transcriptome profiling of the mouse spermatogenic cells in response to DNA alkylation at distinct stages of spermatogenesis. In this study, RNA sequencing (RNA-seq) was performed in pachytene spermatocytes (PS) and round spermatids (RS) at 0 or 30 min following Methyl Methanesulfonate (MMS) treatment and with untreated controls. A large number of differentially expressed genes (DEGs) were identified by comparison of the three groups in PS and RS, respectively. Functional analyses of all DEGs highlighted the protein ubiquitination pathway and DNA damage response (DDR) network being the two main biological processes in common in the two cell types. Further analyses of the DEGs with 2-fold or more changes between 30 min repair and control group indicated that several cytokine signaling pathways were the most strongly affected in PS and DDR related pathways in RS, respectively. Gene ontology (GO) analyses directly showed differential biological process (BP) affected between PS and RS, with “regulation of transcription” being most overrepresented in PS and “cellular response to stress” in RS, respectively. Moreover, 374 DDR-related genes in PS and 158 in RS among all DEGs were filtered and clustered, which showed dynamic expression patterns in PS and RS. Our analyses provide a transcriptional landscape for male germ cells in response to MMS during spermatogenesis.