Tani Hidenori, Takeshita Jun-Ichi, Aoki Hiroshi, Abe Ryosuke, Toyoda Akinobu, Endo Yasunori, Miyamoto Sadaaki, Gamo Masashi, Torimura Masaki
Environmental Management Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 16-1 Onogawa, Tsukuba, Ibaraki 305-8569, Japan.
Research Institute of Science for Safety and Sustainability, National Institute of Advanced Industrial Science and Technology (AIST), 16-1 Onogawa, Tsukuba, Ibaraki 305-8569, Japan.
J Biosci Bioeng. 2016 Sep;122(3):329-33. doi: 10.1016/j.jbiosc.2016.02.007. Epub 2016 Mar 12.
Because of the limitations of whole animal testing approaches for toxicological assessment, new cell-based assay systems have been widely studied. In this study, we focused on two biological products for toxicological assessment: mouse embryonic stem cells (mESCs) and long noncoding RNAs (lncRNAs). mESCs possess the abilities of self-renewal and differentiation into multiple cell types. LlncRNAs are an important class of pervasive non-protein-coding transcripts involved in the molecular mechanisms associated with responses to chemicals. We exposed mESCs to p-dichlorobenzene (p-DCB) for 1 or 28 days (daily dose), extracted total RNA, and performed deep sequencing analyses. The genome-wide gene expression analysis indicated that mechanisms modulating proteins occurred following acute and chronic exposures, and mechanisms modulating genomic DNA occurred following chronic exposure. Moreover, our results indicate that three novel lncRNAs (Snora41, Gm19947, and Scarna3a) in mESCs respond to p-DCB exposure. We propose that these lncRNAs have the potential to be surrogate indicators of p-DCB responses in mESCs.
由于用于毒理学评估的全动物试验方法存在局限性,新的基于细胞的检测系统已得到广泛研究。在本研究中,我们聚焦于两种用于毒理学评估的生物制品:小鼠胚胎干细胞(mESCs)和长链非编码RNA(lncRNAs)。mESCs具有自我更新和分化为多种细胞类型的能力。LlncRNAs是一类重要的广泛存在的非蛋白质编码转录本,参与与化学物质反应相关的分子机制。我们将mESCs暴露于对二氯苯(p-DCB)1天或28天(每日剂量),提取总RNA,并进行深度测序分析。全基因组基因表达分析表明,急性和慢性暴露后发生了调节蛋白质的机制,慢性暴露后发生了调节基因组DNA的机制。此外,我们的结果表明,mESCs中的三种新型lncRNAs(Snora41、Gm19947和Scarna3a)对p-DCB暴露有反应。我们认为这些lncRNAs有可能成为mESCs中p-DCB反应的替代指标。