Lazar-Contes Irina, Arzate-Mejia Rodrigo G, Tanwar Deepak K, Steg Leonard C, Uzel Kerem, Feudjio Olivier Ulrich, Crespo Marion, Germain Pierre-Luc, Mansuy Isabelle M
Laboratory of Neuroepigenetics, Brain Research Institute, Medical Faculty of the University of Zurich and Institute for Neuroscience, Department of Health Science and Technology of the ETH Zurich, Zurich, Switzerland.
Center for Neuroscience Zurich, ETH and University Zurich, Zurich, Switzerland.
Elife. 2025 Apr 15;12:RP91528. doi: 10.7554/eLife.91528.
In mammals, spermatogonial cells (SPGs) are undifferentiated male germ cells in testis that are quiescent until birth and then self-renew and differentiate to produce spermatogenic cells and functional sperm from early postnatal life throughout adulthood. The transcriptome of SPGs is highly dynamic and timely regulated during postnatal development. We examined if such dynamics involves changes in chromatin organization by profiling the transcriptome and chromatin accessibility of SPGs from early postnatal stages to adulthood in mice using deep RNA-seq, ATAC-seq and computational deconvolution analyses. By integrating transcriptomic and epigenomic features, we show that SPGs undergo massive chromatin remodeling during postnatal development that partially correlates with distinct gene expression profiles and transcription factors (TF) motif enrichment. We identify genomic regions with significantly different chromatin accessibility in adult SPGs that are marked by histone modifications associated with enhancers and promoters. Some of the regions with increased accessibility correspond to transposable element subtypes enriched in multiple TFs motifs and close to differentially expressed genes. Our results underscore the dynamics of chromatin organization in developing germ cells and complement existing datasets on SPGs by providing maps of the regulatory genome at high resolution from the same cell populations at early postnatal, late postnatal and adult stages collected from single individuals.
在哺乳动物中,精原细胞(SPGs)是睾丸中未分化的雄性生殖细胞,在出生前处于静止状态,出生后开始自我更新并分化,从出生后早期直至成年期产生生精细胞和功能性精子。精原细胞的转录组在出生后发育过程中高度动态且受到及时调控。我们通过使用深度RNA测序、ATAC测序和计算反卷积分析,对小鼠从出生后早期到成年期的精原细胞转录组和染色质可及性进行分析,以研究这种动态变化是否涉及染色质组织的改变。通过整合转录组学和表观基因组学特征,我们发现精原细胞在出生后发育过程中经历了大规模的染色质重塑,这与不同的基因表达谱和转录因子(TF)基序富集部分相关。我们鉴定出成年精原细胞中染色质可及性显著不同的基因组区域,这些区域以与增强子和启动子相关的组蛋白修饰为特征。一些可及性增加的区域对应于富含多种TF基序且靠近差异表达基因的转座子亚型。我们的结果强调了发育中的生殖细胞中染色质组织的动态变化,并通过提供来自单个个体在出生后早期、出生后晚期和成年期相同细胞群体的高分辨率调控基因组图谱,补充了现有的精原细胞数据集。