Wang Min, Zhao Wene, Wang Fuqiang, Ling Xiufeng, Chen Daozhen, Zhou Tao, Wang Ying
Centre for Reproductive Medicine, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi 214002, China.
Analytical and Testing Center, Nanjing Medical University, Nanjing 210004, China.
Stem Cells Int. 2018 Jul 8;2018:5842714. doi: 10.1155/2018/5842714. eCollection 2018.
Spermatogonial stem cells (SSCs) are exquisitely regulated to reach a balance between proliferation and differentiation in the niche of seminiferous epithelium. Several extrinsic factors such as GDNF are reported to switch the transition, activating various intrinsic signaling pathways. Transcriptomics analysis could provide a comprehensive landscape of gene expression and regulation. Here, we reanalyzed a previously published transcriptome of two cell types (standing for self-renewing and differentiating SSCs correspondingly). First, we proposed a new parameter, the expression index, to sort the genes considering both absolute and relative expression levels. Using a dynamic statistical model, we identified a list of 1119 candidate genes for SSC self-renewal with the best enrichment of canonical markers. Finally, based on interaction relations, we further optimized the list and constructed a refined network containing integrated information of interactions, expression alternations, biological functions, and disease associations. Further annotation of the 521 refined genes involved in the network revealed an enrichment of well-studied signaling pathways. We believe that the refined network could help us better understand the regulation of SSCs' fates, as well as find novel regulators or targets for SSC self-renewal or preservation of male fertility.
精原干细胞（SSCs）受到精确调控，以在生精上皮微环境中实现增殖与分化之间的平衡。据报道，几种外在因素如胶质细胞源性神经营养因子（GDNF）可转换这种转变，激活各种内在信号通路。转录组学分析能够提供基因表达和调控的全面概况。在此，我们重新分析了先前发表的两种细胞类型（分别代表自我更新和分化的SSCs）的转录组。首先，我们提出了一个新参数——表达指数，用于综合考虑绝对和相对表达水平对基因进行分类。使用动态统计模型，我们鉴定出了1119个用于SSC自我更新的候选基因列表，这些基因对典型标志物的富集效果最佳。最后，基于相互作用关系，我们进一步优化了该列表，并构建了一个包含相互作用、表达变化、生物学功能和疾病关联等综合信息的精细网络。对网络中涉及的521个精细基因的进一步注释揭示了一些研究充分的信号通路的富集情况。我们相信，这个精细网络能够帮助我们更好地理解SSCs命运的调控机制，以及找到用于SSC自我更新或维持男性生育能力的新调节因子或靶点。
