title: Genome-wide gene expression analysis of mouse embryonic stem cells exposed to p-dichlorobenzene.
abstract: 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.
authors.affiliation: Environmental Management Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 16-1 Onogawa, Tsukuba, Ibaraki 305-8569, Japan. Electronic address: h.tani@aist.go.jp.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Tani
authors.affiliation: 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.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Takeshita
authors.affiliation: Environmental Management Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 16-1 Onogawa, Tsukuba, Ibaraki 305-8569, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Aoki
authors.affiliation: College of Engineering Systems, School of Science and Engineering, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Abe
authors.affiliation: College of Engineering Systems, School of Science and Engineering, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573, Japan.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Toyoda
authors.affiliation: Department of Risk Engineering, Faculty of Systems and Information Engineering, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Endo
authors.affiliation: Department of Risk Engineering, Faculty of Systems and Information Engineering, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573, Japan.
authors.forename: Sadaaki
authors.initials: S
authors.lastname: Miyamoto
authors.affiliation: 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.
authors.forename: Masashi
authors.initials: M
authors.lastname: Gamo
authors.affiliation: Environmental Management Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 16-1 Onogawa, Tsukuba, Ibaraki 305-8569, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Torimura
mesh_terms: D000818:Animals; D002722:Chlorobenzenes / Q000008:administration & dosage / Q000633:toxicity*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D005819:Genetic Markers / Q000235:genetics; D016678:Genome / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000032:analysis / Q000235:genetics / Q000302:isolation & purification; D013997:Time Factors; D018675:Toxicity Tests
chemical_list: D002722:Chlorobenzenes; D005819:Genetic Markers; D062085:RNA, Long Noncoding; C018511:4-dichlorobenzene
keywords: Deep sequencing; Mouse embryonic stem cells; Non-coding RNA; Toxicological assessment; p-Dichlorobenzene