Drawing a differentiation potency index of iPSC based on genomic imprinting

2013 Fiscal Year Final Research Report

• Project/Area Number: 23659181
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Human genetics
• Research Institution: Saga University
• Principal Investigator: SOEJIMA Hidenobu 佐賀大学, 医学部, 教授 (30304885)
• Co-Investigator(Renkei-kenkyūsha): OGURA Atsuo 独立行政法人理化学研究所, 遺伝工学基盤技術室, 室長 (20194524)
• Project Period (FY): 2011 – 2013
• Keywords: エピジェネティクス / ゲノム刷り込み / iPS細胞 / 肝芽腫

Research Abstract

To evaluate iPSC from the aspect of genomic imprinting, we analyzed DNA methylation status of imprinting related differentially methylated regions (DMRs), which were scattered throughout the genome, in iPSCs derived from mouse fibroblast, peripheral blood cells of normal human and Beckwith-Wiedemann syndrome patients. We also analyzed hepatoblastomas, which originated from immature liver precursor cells. We found that in mouse iPSC, the methylation status of many DMRs decreased after reprogramming and that a certain number of DMRs restored their methylation status during retinoic acid induced differentiation. Human iPSC showed that methylation patterns of several DMRs changed to paternal epigenotype after reprogramming. Finally, hepatoblastoma analysis suggested that the occurrence of hypomethylation at a few DMRs prior to tumor development.

Research Products

• [Journal Article] Premature termination of reprogramming in vivo leads to cancer development through altered epigenetic regulation (2014)
  • Author(s): Ohnishi K, Semi K, Yamamoto T, Shimizu M, Tanaka A, Mitsunaga K, Okita K, Osafune K, Arioka Y, Maeda T, Soejima H, Moriwaki H, Yamanaka S, Woltjen K, Yamada Y
  • Journal Title: Cell Volume: 156(4) Pages: 663-677
  • Peer Reviewed
• [Journal Article] A novel de novo point mutation of the OCT-binding site in the IGF2/H19-imprinting control region in a Beckwith-Wiedemann syndrome patient (2013)
  • Author(s): Higashimoto K, Jozaki K, Kosho T, Matsubara K, Fuke T, Yamada D, Yatsuki H, Maeda T, Ohtsuka Y, Nishioka K, Joh K, Koseki H, Ogata T, Soejima H
  • Journal Title: Clin Genet Volume: (published online)
  • Peer Reviewed
• [Journal Article] Comprehensive analyses of imprinted differentially methylated regions reveal epigenetic and genetic characteristics in hepatoblastoma (2013)
  • Author(s): Rumbajan JM, Maeda T, Souzaki R, Mitsui K, Higashimoto K, Nakabayashi K, Yatsuki H, Nishioka K, Harada R, Aoki S, Kohashi K, Oda Y, Hata K, Saji T, Taguchi T, Tajiri T, Soejima H, Joh K
  • Journal Title: BMC Cancer Volume: 13 Pages: 608
  • Peer Reviewed
• [Journal Article] Ash1l methylates Lys36 of histone H3 independently of transcriptional elongation to counteract Polycomb silencing (2013)
  • Author(s): Miyazaki H, Higashimoto K, Yada Y, A. Endo T¶, Sharif J¶, Komori T, Matsuda M, Koseki Y, Nakayama M, Soejima H, Handa H, Koseki H, Hirose S, Nishioka K
  • Journal Title: PLoS Genet Volume: 9(11) Pages: e1003897
  • Peer Reviewed
• [Journal Article] Homozygous deletion of DIS3L2 exon 9 due to non-allelic homologous recombination between LINE-1s in a Japanese patient with Perlman syndrome (2013)
  • Author(s): Higashimoto K, Maeda T, Okada J, Ohtsuka Y, Sasaki K, Hirose A, Nomiyama M, Takayanagi T, Fukuzawa R, Yatsuki H, Koide K, Nishioka K, Joh K, Watanabe Y, Yoshiura KI, Soejima H
  • Journal Title: Eur J Hum Genet Volume: 21(11) Pages: 1316-1319
  • Peer Reviewed
• [Journal Article] Epigenetic and genetic alterations of the imprinting disorder Beckwith-Wiedemann syndrome and related disorders (2013)
  • Author(s): Soejima H, Higashimoto K
  • Journal Title: J Hum Genet Volume: 58(7) Pages: 402-409
  • Peer Reviewed
• [Journal Article] Regional DNA methylation differences between humans and chimpanzees are associated with genetic changes, transcriptional divergence and disease genes (2013)
  • Author(s): Fukuda K, Ichiyanagi K, Yamada Y, Go Y, Udono T, Wada S, Maeda T, Soejima H, Saitou N, Ito T, Sasaki H
  • Journal Title: J Hum Genet Volume: 58(7) Pages: 446-454
  • Peer Reviewed
• [Journal Article] Congenital hyperinsulinism in an infant with paternal uniparental disomy on chromosome 11p15 : Few clinical features suggestive of Beckwith-Wiedemann syndrome (2013)
  • Author(s): Adachi H, Takahashi I, Higashimoto K, Tsuchida S, Noguchi A, Tamura H, Arai H, Ito T, Masue M, Nishibori H, Takahashi T, Soejima H
  • Journal Title: Endocr J Volume: 60(4) Pages: 403-408
  • Peer Reviewed
• [Journal Article] Novel Mutations of CDKN1C in Japanese Patients with Beckwith-Wiedemann Syndrome (2013)
  • Author(s): Yatsuki H, Higashimoto K, Jozaki K, Koide K, Okada J, Watanabe Y, Okamoto N, Tsuno Y, Yoshida Y, Ueda K, Shimizu K, Ohashi H, Mukai T, Soejima H
  • Journal Title: Genes & Genomics Volume: 35(2) Pages: 141-147
  • Peer Reviewed
• [Journal Article] Beckwith-Wiedemann 症候群とSilver-Russell 症候群 (2013)
  • Author(s): 前田寿幸, 東元健, 副島英伸
  • Journal Title: 小児科臨床 Volume: 66(増刊号) Pages: 1308-1314
• [Journal Article] Beckwith-Wiedemann 症候群, Sotos 症候群 (2013)
  • Author(s): 副島英伸
  • Journal Title: 周産期医学 Volume: 43(3) Pages: 377-382
• [Journal Article] Characterization of DNA methylation errors in patients with imprinting disorders conceived by assisted reproduction technologies (2012)
  • Author(s): Hiura H, Okae H, Miyauchi N, Sato F, Sato A, Van De Pette M, John RM, Kagami M, Nakai K, Soejima H, Ogata T, Arima T
  • Journal Title: Hum Reprod Volume: 27(8) Pages: 2541-2548
  • Peer Reviewed
• [Journal Article] Aberrant methylation of H19-DMR acquired after implantation was dissimilar in soma versus placenta of patients with Beckwith-Wiedemann syndrome (2012)
  • Author(s): Higashimoto K, Nakabayashi K, Yatsuki H, Yoshinaga H, Jozaki K, Okada J, Watanabe Y, Aoki A, Shiozaki A, Saito S, Koide K, Mukai T, Hata K, Soejima H
  • Journal Title: Am J Med Genet Part A Volume: 158A(7) Pages: 1670-1675
  • Peer Reviewed
• [Presentation] Beckwith-Wiedemann 症候群と関連疾患におけるゲノム・エピゲノム異常 (2013)
  • Author(s): 副島英伸
  • Organizer: 日本人類遺伝学会第58回大会「シンポジウム8 先天異常とゲノム・エピゲノム」
  • Place of Presentation: 仙台
  • Year and Date: 20131120-23
• [Presentation] シスチン尿症を伴うゲノムワイド父性片親性ダイソミー症例の遺伝子解析 (2013)
  • Author(s): 大塚泰史, 佐々木健作, 城崎幸介, 東元健, 岡本信彦, 高間勇一, 窪田昭男, 松本富美, 中山雅弘, 吉浦孝一郎, 副島英伸
  • Organizer: 日本人類遺伝学会第58回大会
  • Place of Presentation: 仙台
  • Year and Date: 20131120-23
• [Presentation] H19DMR メチル化異常で発症するインプリント疾患におけるH19DMR の変異解析 (2013)
  • Author(s): 東元 健, 城崎幸介, 八木ひとみ, 古庄知己, 松原圭子, 山田大輔, 前田寿幸, 大塚泰史, 古関明彦, 緒方勤, 副島英伸
  • Organizer: 第7回日本エピジェネティクス研究会年会
  • Place of Presentation: 奈良
  • Year and Date: 20130530-31
• [Presentation] Beckwith-Wiedemann 症候群におけるインプリントDMR のマルチローカスメチル化解析 (2013)
  • Author(s): 前田寿幸, 東元健, 中林一彦, 城崎幸介, 八木ひとみ, 緒方勤, 秦健一郎, 副島英伸
  • Organizer: 第7回日本エピジェネティクス研究会年会
  • Place of Presentation: 奈良
  • Year and Date: 20130530-31
• [Presentation] Ash1l methylates Lys36 of histone H3 independently of transcriptional elongation to counteract Polycomb silencing (2013)
  • Author(s): 宮崎仁美, 東元 健, 矢田有加里, 遠藤高帆, Sharif Jafar, 小森敏治, , 松田正史, 古関庸子, 中山学, 副島英伸, 半田宏, 古関明彦, 広瀬進, 西岡憲一
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2013-03-06
• [Presentation] H19-DMR メチル化異常で発症するインプリント疾患におけるH19-DMR の変異解析 (2012)
  • Author(s): 東元 健, 城崎幸介, 八木ひとみ, 古庄知己, 松原圭子, 山田大輔, 前田寿幸, 大塚泰史, 古関明彦, 緒方勤, 副島英伸
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 20121211-14
• [Presentation] Genome-wide Screening of Aberrant Methylations of Imprinted DMRs in Hepatoblastomas (2012)
  • Author(s): Rumbajan JM, Maeda T, Tajiri T, Higashimoto K, Souzaki R, Taguchi T, Soejima H, Joh K
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 20121211-14
• [Presentation] Genome-wide quantitative DNA methylation analysis of imprinted DMRs in patients with Beckwith-Wiedemann Syndrome by MALDI-TOF MS technology (2012)
  • Author(s): Maeda T, Jozaki K, Yatsuki H, Higashimoto K, Soejima H
  • Organizer: The American Society of Human Genetics 62nd Annual Meeting (poster 3432T)
  • Place of Presentation: San Francisco, California, USA
  • Year and Date: 20121106-10
• [Presentation] The relationship between paternal uniparental disomy and clinical features in patients with Beckwith-Wiedemann syndrome (2012)
  • Author(s): Ohtsuka Y, Jozaki K, Maeda T, Yatsuki H, Higashimoto K, Soejima H
  • Organizer: The American Society of Human Genetics 62nd Annual Meeting (poster 3519T)
  • Place of Presentation: San Francisco, California, USA
  • Year and Date: 20121106-10
• [Presentation] Beckwith-Wiedemann 症候群における片親性父性ダイソミーの多様性と臨床症状との関連 (2012)
  • Author(s): 大塚泰史, 城崎幸介, 前田寿幸, 八木ひとみ, 東元 健, 副島英伸
  • Organizer: 日本人類遺伝学会第57回大会
  • Place of Presentation: 東京
  • Year and Date: 20121024-27
• [Presentation] 肝芽腫におけるメチル化インプリントDMR のゲノムワイド検索 (2012)
  • Author(s): 副島英伸, 東元 健, 田尻達郎
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌市
  • Year and Date: 20120919-21
• [Presentation] 本邦Beckwith-Wiedemann 症候群の臨床像とゲノム・エピゲノム解析.180 超例の解析により明らかとなった本邦Beckwith-Wiedemann 症候群の臨床像とゲノム・エピゲノム変異 (2011)
  • Author(s): 副島英伸, 城崎幸介, 八木ひとみ, 前田寿幸, 大塚泰史, 東元 健
  • Organizer: 日本人類遺伝学会第56回大会 第11回東アジア人類遺伝学会
  • Place of Presentation: 幕張
  • Year and Date: 20111109-12
• [Presentation] Acquisition of aberrant hypermethylation after implantation induces discordant hypermethylation at H19-DMR between bodies and placentas in Beckwith-Wiedemann syndrome patients (2011)
  • Author(s): Soejima H, Nakabayashi K, Yatsuki H, Jozaki K, Hata K, Higashimoto K
  • Organizer: Idibell Cancer Conferences on Imprinting and Beyond; "Mono-allelic expression in Health and Disease"
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 20110921-23
• [Book] Beckwith-Wiedemann症候群と小児腫瘍.遺伝子医学MOOK25エピジェネティクスと病気 第2 章エピジェネティクスと病気 4.不妊・先天異常(監修:佐々木裕之, 編集:中尾光善, 中島欽一) (2013)
  • Author(s): 東元健, 副島英伸
  • Total Pages: 195-201
  • Publisher: メディカルドゥ, 大阪
• [Book] ベックウィズ・ヴィーデマン症候群 第XIV 章 先天異常・奇形 症候群ハンドブック.(井村裕夫総編集, 福井次矢・辻省次編集.) (2011)
  • Author(s): 副島英伸
  • Total Pages: 679
  • Publisher: 中山書店
• [Book] シルバー・ラッセル症候群第XIV 章 先天異常・奇形 症候群ハンドブック.(井村裕夫総編集, 福井次矢・辻省次編集) (2011)
  • Author(s): 副島英伸
  • Total Pages: 685
  • Publisher: 中山書店
• [Remarks] ホームページ
  • URL: http://www.biomol.med.saga-u.ac.jp/mbg/index.htm