Studies on developmental programs of embryonic stem cells and germ cells in mice

2012 Fiscal Year Final Research Report

• Project Area: The germline: its developmental cycle and epigenome network
• Project/Area Number: 20062013
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: ABE Kuniya 独立行政法人理化学研究所, 動物変異動態解析技術開発チーム, チームリーダー (40240915)
• Co-Investigator(Kenkyū-buntansha): MISE Natan 独立行政法人理化学研究所, 動物変異動態解析技術開発チーム, 開発研究員 (00360644) ; SUGIMOTO Michihiko 独立行政法人理化学研究所, 動物変異動態解析技術開発チーム, 開発研究員 (10373317) ; FUCHIKAMI Takuya 独立行政法人理化学研究所, 動物変異動態解析技術開発チーム, 開発研究員 (00392100)
• Project Period (FY): 2008 – 2012
• Keywords: 始原生殖細胞 / ゲノム再プログラム化 / 遺伝子発現 / エピゲノム / DNA メチル化 / 癌精巣抗原遺伝子

Research Abstract

We have analyzed gene expression profiles and DNA methylation profiles of cells belong to the cell lineage from pluripotent cells in the blastocyst to primordial germ cells to spermatogonia or oocytes in the mouse. We also investigated changes in X chromosome inactivation status of female cells in this lineage or changes in nuclear architecture during development of these cells. Through these analyses, we gained comprehensive understanding of genes functioning in this cell lineage, and identified developmental transition points in this lineage revealed by large scale changes in gene expression and epigenetic states. We also identified large DNA domains hypomethylated specifically in male germ cells possibly involved in expression regulation of genes contained in these domains. Using a spontaneous developmental mutant affecting one of developmental transitions in this lineage, we found that Vps52 is the essential gene required for growth and differentiation of primitive ectoderm. To achieve the research described above, we developed novel experimental technologies and research resources, which have facilitated active collaborations between research groups belong to this Priority Area.

Research Products

• [Journal Article] Max is a repressor of germ-cell-related gene expression in mouse embryonic stem cells. (2013)
  • Author(s): Maeda, I., Okamura, D., Tokitake, Y., Ikeda, M., Kawaguchi, H., Mise, N., Abe, K., Noce, T., Okuda, A. and Matsui, Y.
  • Journal Title: Nature communications Volume: (in press)
  • DOI: doi:10.1038/ncomms2780.
  • Peer Reviewed
• [Journal Article] Generation of a novel germline stem cell line expressing a germline-specific reporter in the mouse. (2013)
  • Author(s): Shiura, H., Ikeda, R., Lee, J., Sato, T., Ogonuki, N., Hirose, M., Ogura, A., Ogawa, T., Abe, K.
  • Journal Title: genesis Volume: (in press)
  • Peer Reviewed
• [Journal Article] RNAi-mediated knockdown of Xist does not rescue the impaired development of female cloned mouse embryos. (2013)
  • Author(s): Oikawa. M. Matoba, S., Inoue, K., Kamimura, S., Hirose, M., Ogonuki, N., Shiura, H., Sugimoto, M., Abe, K., Ishino, F. and Ogura, A.
  • Journal Title: J. Repord. Dev. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Ectopic expression of Ptf1a induces spinal defects, urogenital defects and anorectal malformations in Danforth's short tail mice. (2012)
  • Author(s): Semba, K., Araki, K., Matsumoto, K.-I., Suda, H., Ando, T. Sei, A., Mizuta, H., Takagi, K., Nakahara, M., Muta, M., Yamada, G., Nakagata, N., Iida, A., Ikegawa, Y., Araki, M., Abe, K. and Yamamura, K.
  • Journal Title: PLoS Genet. Volume: Vol.9 Pages: e1003204
  • DOI: doi: 10.1371/journal.pgen.1003204.
  • Peer Reviewed
• [Journal Article] Molecular identification of t^<w5>: Vps52 promotes pluripotential cell differentiation through cell-cell interactions. (2012)
  • Author(s): Sugimoto, M., Kondo, M., Hirose, M., Suzuki, M., Mekada, K., Abe, T., Kiyonari, H., Ogura, A., Takagi, N., Artzt, K. and Abe, K.
  • Journal Title: Cell Reports Volume: Vol.2 Pages: 1363-1374
  • DOI: doi:10.1016/j.celrep.2012.10.004.
  • Peer Reviewed
• [Journal Article] Cell-cycle gene-specific control of transcription has a critical role in proliferation of primordial germ cells. (2012)
  • Author(s): Okamura, D., Maeda, I., Taniguchi, H., Tokitake, Y., Ikeda, M., Ozato, K., Mise, N., Abe, K., Noce, T., Belmonte, J.C.I.,Matsui, Y.
  • Journal Title: Genes Dev. Volume: Vol.26 Pages: 2477-2482
  • Peer Reviewed
• [Journal Article] RNAi-mediated knockdown of Xist can rescue the impaired postimplantation development of cloned mouse embryos. (2011)
  • Author(s): Matoba, S., Inoue, K., Kohda, T., Sugimoto, M., Mizutani, E., Ogonuki, N., Nakamura, T., Abe, K., Nakano, T., Ishino, F. and Ogura, A.
  • Journal Title: Proc. Natn. Acad. Sci. USA Volume: Vol.108 Pages: 20621-20626
  • DOI: doi:10.1073/pnas.1112664108.
  • Peer Reviewed
• [Journal Article] Incomplete X-inactivation initiated by a hypomorphic Xist allele in the mouse. (2011)
  • Author(s): Hoki, Y., Ikeda, R., Mise, N., Sakata, Y., Ohhata, T., Sasaki, H., Abe, K., Sado, T.
  • Journal Title: Development Volume: Vol.138 Pages: 2649-2659
  • Peer Reviewed
• [Journal Article] Highly parallel SNP genotyping reveals high-resolution landscape of mono-allelic Ube3a expression associated with locus-wide antisense transcription. (2011)
  • Author(s): Numata, K., Kohama, C., Abe, K., Kiyosawa, H.
  • Journal Title: Nucleic Acids Res Volume: Vol.39 Pages: 2649-2657
  • Peer Reviewed
• [Journal Article] Initiation of trophectoderm lineage specification in mouse embryos is independent of Cdx2. (2010)
  • Author(s): Wu, G., Gentile, L., Fuchikami, T., Sutter, J., Psathaki, K., Esteves, T., Arauzo-Bravo, M.J., Ortmeier, C., Verberk, G., Abe, K., Scholer, H.R.
  • Journal Title: Development Volume: Vol.37 Pages: 4159-4169
  • Peer Reviewed
• [Journal Article] Impeding Xist expression from the active X chromosome improves mouse somatic cell cloning. (2010)
  • Author(s): Inoue, K., Kohda, T., Sugimoto, M., Sado, T., Ogonuki, N., Matoba, S., Shiura, H., Ikeda, R., Mochida, K., Fujii, T., Sawai, K., Otte, A.P., Tian, X.C., Yang, X., Ishino, F., Abe, K. and Ogura, A.
  • Journal Title: Science Volume: Vol.330 Pages: 496-499
  • Peer Reviewed
• [Journal Article] Genome-wide analysis of expression modes and DNA methylation status at sense-antisense transcript loci in mouse. (2010)
  • Author(s): Watanabe, Y., Numata, K., Murata, S., Osada, Y., Saito, R., Nakaoka, H., Yamamoto, N., Watanabe, K., Kato, H., Abe, K. and Kiyosawa, H.
  • Journal Title: Genomics Volume: Vol.96 Pages: 333-341
  • Peer Reviewed
• [Journal Article] Induction of primordial germ cells from mouse induced pluripotent stem cells derived from adult hepatocytes. (2010)
  • Author(s): Imamura, M., Aoi, T., Tokumasu, A., Mise, N., Abe, K., Yamanaka, S., and Noce, T.
  • Journal Title: Molecular Reproduction and Development Volume: Vol.77 Pages: 802-811
  • Peer Reviewed
• [Journal Article] The X-linked imprinted gene family Fthl17 shows predominantly female expression following the two-cell stage in mouse embryos. (2010)
  • Author(s): Kobayashi, S., Fujihara, Y. Mise, N., Kaseda, K., Abe, K., Ishino, F., Okabe, M.
  • Journal Title: Nucleic Acids Res. Volume: Vol.38 Pages: 3672-3681
  • Peer Reviewed
• [Journal Article] Identification of novel endogenous antisense transcripts by DNA microarray analysis targeting complementary strand of annotated genes. (2009)
  • Author(s): Numata, K., Osada, Y., Okada, Y., Saito, R., Hiraiwa, N., Nakaoka, H., Yamamoto, N., Watanabe, K., Okubo, K., Kohama, C., Kanai, A., Abe, K., Kiyosawa, H.
  • Journal Title: BMC Genomics Volume: Vol.10 Pages: 392
  • DOI: doi:10.1186/1471-2164-10-392.
  • Peer Reviewed
• [Journal Article] New evidence confirms that the mitochondrial bottleneck is generated without reduction of mitochondrial DNA content in early primordial germ cells of mice. (2009)
  • Author(s): Cao, L., Shitara, H., Sugimoto, M., Hayashi, J.=I., Abe, K., Yonekawa, H.
  • Journal Title: PLoS genetics Volume: Vol5 Pages: e1000756
  • DOI: doi:10.1371/journal.pgen.1000756.
  • Peer Reviewed
• [Journal Article] A high-speed congenic strategy using first-wave male germ cells. (2009)
  • Author(s): Ogonuki N, Inoue K, Hirose M, Miura I, Mochida K, Sato T, Mise N, Mekada K, Yoshiki A, Abe K, Kurihara H, Wakana S, Ogura A.
  • Journal Title: PLoS One Volume: Vol.4 Pages: e4943
  • DOI: doi:10.1371/journal.pone.0004943.
  • Peer Reviewed
• [Journal Article] Large-scale production of growing oocytes from neonatal mouse ovaries. (2009)
  • Author(s): Honda, A., Hirose, M., Inoue, K., Hiura, H., Miki, H., Ogonuki, N., Sugimoto, M., Abe, K., Kanatsu-Shinohara, M., Kono, T., Shinohara, T., Ogura, A.
  • Journal Title: Int. J. Dev. Biol. Volume: Vol.53 Pages: 605-613
  • Peer Reviewed
• [Journal Article] Natural antisense transcripts are co-expressed with sense mRNAs in synaptoneurosomes of adult mouse forebrain. (2008)
  • Author(s): Smalheiser, N.R., Lugli, G., Torvik, V.I., Mise, N., Ikeda, R., Abe, K.
  • Journal Title: Neurosci Res. Volume: Vol.62 Pages: 236-239
  • Peer Reviewed
• [Journal Article] Differences and similarities in the developmental status of embryo-derived stem cells and primordial germ cells revealed by global expression profiling. (2008)
  • Author(s): Mise, N., Fuchikami, T., Sugimoto, M., Kobayakawa, S., Ike, F., Ogawa, T., Tada, T., Kanaya, S., Noce, T. and Abe, K.
  • Journal Title: Genes to cells Volume: Vol.13 Pages: 863-877
  • Peer Reviewed
• [Journal Article] Comparative expression analysis uncovers novel features of endogenous antisense transcription. (2008)
  • Author(s): Okada, Y., Tashiro, C., Numata, K., Watanabe, K., Nakaoka, H., Yamamoto, N., Okubo, K., Ikeda, R., Saito, R., Kanai, A., Abe, K., Tomita, M., Kiyosawa, H.
  • Journal Title: Human Mol. Genet Volume: Vol.17 Pages: 1631-1640
  • Peer Reviewed
• [Presentation] Xist 発現から見たマウス着床期における細胞リプログラミング (2012)
  • Author(s): 志浦寛相
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-14
• [Presentation] マウス生殖細胞で発現するX連鎖遺伝子群に見出された特徴的なエピジェネティック修飾 (2012)
  • Author(s): 池田理恵子
  • Organizer: 日本遺伝学会第84回大会
  • Place of Presentation: 福岡
  • Year and Date: 2012-09-25
• [Presentation] Region-wide DNA methylation and gene expression of the X-linked genes in mouse germ line. (2011)
  • Author(s): Rieko Ikeda
  • Organizer: 50 Years of X Inactivation Research - 3rd X-inactivation meeting, Oxford 2011
  • Place of Presentation: Oxford (UK)
  • Year and Date: 20110720-24
• [Presentation] Dynamics of epigenomic changes during development of early embryos and primordial germ cells in mice. (2011)
  • Author(s): Kuniya Abe
  • Organizer: 50 Years of X Inactivation Research - 3rd X-inactivation meeting, Oxford 2011
  • Place of Presentation: Oxford (UK)
  • Year and Date: 20110720-24
• [Presentation] マウスIgf2r 遺伝子の刷り込み型発現制御の成立に関わるDNA メチル化のES 細胞を用いた解析 (2010)
  • Author(s): 三瀬名丹
  • Organizer: 遺伝学会第82回大会
  • Place of Presentation: 札幌
  • Year and Date: 2010-09-21
• [Presentation] マウス初期胚・生殖細胞発生におけるエピゲノム動態解析 (2010)
  • Author(s): 阿部訓也
  • Organizer: 遺伝学会第82回大会
  • Place of Presentation: 札幌
  • Year and Date: 2010-09-20
• [Presentation] New evidence confirms that the mitochondrial bottleneck is generated without reduction of mitochondrial DNA content in early primordial germ cells of mice. (2009)
  • Author(s): Liqin Cao
  • Organizer: 6th Conference of Asian Society for Mitochondrial Research and Medicine
  • Place of Presentation: 台北(中華民国)
  • Year and Date: 20091030-1101
• [Presentation] 多能性胚細胞(エピブラスト)の増殖・分化を制御するtw5 遺伝子の同定と機能解析 (2009)
  • Author(s): 阿部訓也
  • Organizer: 文部科学省科学研究費補助金・特定領域研究「生殖系列の世代サイクルとエピゲノムネットワーク」第2回公開シンポジウム
  • Place of Presentation: 品川
  • Year and Date: 2009-11-26
• [Presentation] Establishment of in vitro system for analysis of genomic imprinting using newly isolated ES/EG cell lines. (2009)
  • Author(s): Nathan Mise
  • Organizer: The 24th Naito Conference on Nuclear Dynamics and RNA [II]
  • Place of Presentation: Sapporo (Japan)
  • Year and Date: 2009-06-25
• [Presentation] Essential role of Nanos3 for acquisition of germ cell identity in mice. (2008)
  • Author(s): Kuniya Abe
  • Organizer: 22nd International Mammalian Genome Conference
  • Place of Presentation: Prague (Czech Republic)
  • Year and Date: 2008-11-15
• [Presentation] DNA のメチル化に影響を与える内在性アンチセンス転写産物のスクリーニング (2008)
  • Author(s): 渡邊豊
  • Organizer: 日本遺伝学会第80回大会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-09-04
• [Presentation] ES/EG 細胞試験管内分化系を用いた生殖細胞研究:新規レポーターES/EG細胞の樹立とその分化能の解析 (2008)
  • Author(s): 三瀬名丹
  • Organizer: 日本遺伝学会第80回大会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-09-04
• [Presentation] 雌マウスPGC におけるX 染色体再活性化のタイミングとDNA メチレーションの変化 (2008)
  • Author(s): 杉本道彦
  • Organizer: 日本遺伝学会第80回大会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-09-04
• [Book] 「新しいリサーチツールとしてのバイオイメージング(蛍光イメージングを中心に)」モデル動物利用マニュアル 生物機能モデルと新しいリソース・リサーチツール (2011)
  • Author(s): 阿部訓也
  • Total Pages: 601-610
  • Publisher: エル・アイ・シー
• [Book] 「胚性幹細胞・生殖細胞の発生分化と核内構造動態」実験医学増刊号「細胞核ー遺伝情報制御と疾患」 (2009)
  • Author(s): 阿部訓也
  • Total Pages: 2767-2773
  • Publisher: 羊土社
• [Remarks]
  • URL: http://www.brc.riken.jp/lab/mcd/mcd2/