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農学部 獣医学科 |
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Arai Y., Nishino K.
Journal of Toxicological Sciences 48 ( 11 ) 571 - 583 2023年9月
担当区分：筆頭著者, 責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Toxicological Sciences
Various chemicals, including pesticides, heavy metals, and metabolites of tobacco, have been detected in fetal environment. Fetuses are exposed to these chemicals at relatively low concentrations; however, their risk of developing neurological and behavioral disorders increases after birth. We aimed to evaluate the effects of five chemicals (diethylphosphate, cotinine, octachlorodipropyl ether, mercury, and selenium) detected in the serum of pregnant mothers on neural development using human neurospheres (NSphs) differentiated from induced pluripotent stem cells. Exposure to each chemical at serum concentrations revealed no effects on NSph development. However, combined exposure to the five chemicals caused a significant decrease in NSph size and altered gene expression and neural differentiation. Thus, we next focused on DNA methylation to investigate changes in NSph properties caused by chemical exposure. Combined exposure to chemicals had extremely small effects on the DNA methylation status of NSphs at individual gene loci. However, stochastic changes in methylation status caused by chemical exposure were significantly accumulated throughout the entire genome. These results suggest that the five chemicals acted as epimutagens that alter the epigenetic status during human neural development at the biological level. Taken together, we showed for the first time, the epimutagen-induced alterations in neural differentiation at serum concentrations using an in vitro human neuronal model.
DOI： 10.2131/jts.48.571
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Sekiya A., Takasawa K., Arai Y., Horike S.i., Akutsu H., Umezawa A., Nishino K.
Regenerative Therapy 21 620 - 630 2022年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Regenerative Therapy
Introduction: Human induced pluripotent stem cells (hiPSCs) are useful tools for reproducing neural development in vitro. However, each hiPSC line has a different ability to differentiate into specific lineages, known as differentiation propensity, resulting in reduced reproducibility and increased time and funding requirements for research. To overcome this issue, we searched for predictive signatures of neural differentiation propensity of hiPSCs focusing on DNA methylation, which is the main modulator of cellular properties. Methods: We obtained 32 hiPSC lines and their comprehensive DNA methylation data using the Infinium MethylationEPIC BeadChip. To assess the neural differentiation efficiency of these hiPSCs, we measured the percentage of neural stem cells on day 7 of induction. Using the DNA methylation data of undifferentiated hiPSCs and their measured differentiation efficiency into neural stem cells as the set of data, and HSIC Lasso, a machine learning-based nonlinear feature selection method, we attempted to identify neural differentiation-associated differentially methylated sites. Results: Epigenome-wide unsupervised clustering cannot distinguish hiPSCs with varying differentiation efficiencies. In contrast, HSIC Lasso identified 62 CpG sites that could explain the neural differentiation efficiency of hiPSCs. Features selected by HSIC Lasso were particularly enriched within 3 Mbp of chromosome 5, harboring IRX1, IRX2, and C5orf38 genes. Within this region, DNA methylation rates were correlated with neural differentiation efficiency and were negatively correlated with gene expression of the IRX1/2 genes, particularly in female hiPSCs. In addition, forced expression of the IRX1/2 impaired the neural differentiation ability of hiPSCs in both sexes. Conclusion: We for the first time showed that the DNA methylation state of the IRX1/2 genes of hiPSCs is a predictive biomarker of their potential for neural differentiation. The predictive markers for neural differentiation efficiency identified in this study may be useful for the selection of suitable undifferentiated hiPSCs prior to differentiation induction.
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Nishino K, Arai Y 他
Human Cell 34 ( 1 ) 99 - 110 2021年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Human Cell
The use of human induced pluripotent stem cells (iPSCs), used as an alternative to human embryonic stem cells (ESCs), is a potential solution to challenges, such as immune rejection, and does not involve the ethical issues concerning the use of ESCs in regenerative medicine, thereby enabling developments in biological research. However, comparative analyses from previous studies have not indicated any specific feature that distinguishes iPSCs from ESCs. Therefore, in this study, we established a linear classification-based learning model to distinguish among ESCs, iPSCs, embryonal carcinoma cells (ECCs), and somatic cells on the basis of their DNA methylation profiles. The highest accuracy achieved by the learned models in identifying the cell type was 94.23%. In addition, the epigenetic signature of iPSCs, which is distinct from that of ESCs, was identified by component analysis of the learned models. The iPSC-specific regions with methylation fluctuations were abundant on chromosomes 7, 8, 12, and 22. The method developed in this study can be utilized with comprehensive data and widely applied to many aspects of molecular biology research.
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Dog steroidogenic factor-1: molecular cloning and analysis of epigenetic regulation.
Sekiya A, Takasawa K, Arai Y, Torisu S, Nishino K
The Journal of veterinary medical science 2020年4月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：公益社団法人 日本獣医学会
Steroidogenic factor 1 (SF-1) is a nuclear receptor that is important in steroid hormone production, and adrenal and gonad development. The <i>SF-1</i> gene is highly conserved among most vertebrates. However, dog <i>SF-1</i> registered in public databases, such as CanFam3.1, lacks the 5′ end compared to other mammals including mouse, human, bovine, and cat. Whether this defect is due to species differences or database error is unclear. Here, we determined the full-length dog <i>SF-1</i> cDNA sequence and identified the missing 5′ end sequence in the databases. The coding region of the dog <i>SF-1</i> gene has 1,386 base pairs, and the protein has 461 amino acid residues. Sequence alignment analysis among vertebrates revealed that the 5′ end sequence of dog <i>SF-1</i> cDNA is highly conserved compared to other vertebrates. The genomic position of the first exon was determined, and its promoter region sequence was analyzed. The DNA methylation state at the basal promoter and the expression of dog <i>SF-1</i> in steroidogenic tissues and non-steroidogenic cells were examined. CpG sites at the basal promoter displayed methylation kinetics inversely correlated with gene expression. The promoter was hypomethylated and hypermethylated in <i>SF-1</i> expressing and non-<i>SF-1</i> expressing tissues, respectively. In conclusion, we identified the true full sequence of dog <i>SF-1 </i>cDNA and determined the genome sequence around the first exon. The gene is under the control of epigenetic regulation, such as DNA methylation, at the promoter.
DOI： 10.1292/jvms.20-0050
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DNA methylation ambiguity in the Fibrillin-1 (FBN1) CpG island shore possibly involved in Marfan syndrome.
Arai Y, Umeyama K, Okazaki N, Nakano K, Nishino K, Nagashima H, Ohgane J
Scientific reports 10 ( 1 ) 5287 2020年3月
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疾患治療におけるエピゲノムの可能性：再生医療を見据えたiPS細胞研究の新たなパラダイム
新井良和、西野光一郎
mRNA 2023年2月
掲載種別：記事・総説・解説・論説等（学術雑誌）
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再生医療に向けたエピゲノムによるiPS細胞の特性解析 招待あり
新井 良和, 西野 光一郎
遺伝子医学 10 ( 1 ) 61 - 67 2020年
記述言語：日本語 掲載種別：記事・総説・解説・論説等（学術雑誌）
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機械学習とiPS細胞研究から得られるバイオビッグデータの融合 招待あり
高澤建,新井良和,西野光一郎
再生医療開発 2019年
記述言語：日本語 掲載種別：記事・総説・解説・論説等（学術雑誌）
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ハプロ不全優性遺伝病発症の新たな視点：分子メカニズムとしてエピジェネティクスが関与する可能性 招待あり
竹内 健太, 牧野 智宏, 新井 良和, 大鐘潤
明治大学農学部研究報告 65 ( 4 ) 96 - 103 2016年
記述言語：日本語 掲載種別：記事・総説・解説・論説等（大学・研究所紀要）
講演・口頭発表等 【 表示 ／ 非表示 】
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ヒト雄性iPS細胞における活性X染色体のDNAメチル化動態の解析
富田清良, 新井良和, 西野光一郎 他
第113回日本繁殖生物学会大会
開催年月日： 2020年9月23日 - 2020年9月25日
記述言語：日本語 会議種別：ポスター発表
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免疫不全疑い犬における遺伝子診断：CD40 Ligandの点変異の同定
森正太郎, 新井良和, 西野光一郎 他
第162回日本獣医学会学術集会
開催年月日： 2019年9月10日 - 2019年9月12日
記述言語：日本語 会議種別：口頭発表（一般）
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多能性を有するイヌiPS細胞の樹立と特性解析
西本光佑, 新井良和, 西野光一郎
第162回日本獣医学会学術集会
開催年月日： 2019年9月10日 - 2019年9月12日
記述言語：日本語 会議種別：口頭発表（一般）
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ハプロ不全優性遺伝病の解明に向けたアリルごとのDNAメチル化解析：フィブリリン1遺伝子を例として
新井良和, 梅山一大, 岡崎なつみ, 西野光一郎, 長嶋比呂志, 大鐘潤
日本エピジェネティクス研究会
開催年月日： 2019年
記述言語：日本語 会議種別：ポスター発表
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TERT-DMRの高メチル化は核ラミナとの結合を介してTERT発現獲得に寄与する
高澤建, 新井良和, 西野光一郎 他
第12回 日本エピジェネティクス研究会年会
開催年月日： 2018年5月24日 - 2018年5月25日
記述言語：日本語 会議種別：口頭発表（一般）
科研費（文科省・学振・厚労省）獲得実績 【 表示 ／ 非表示 】
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エピジェネティック情報に基づく化学物質による脂肪細胞肥大化のリスク評価
研究課題/領域番号：16K16193 2016年04月 - 2018年03月
科学研究費補助金 若手研究(B)
担当区分：研究代表者
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ガラス化凍結技術を応用した膵ランゲルハンス島シート超低温保存法と機能評価法の開発
研究課題/領域番号：15K15480 2015年04月 - 2017年03月
科学研究費補助金 挑戦的萌芽研究
長屋昌樹、新井良和