Analysis of functions of a large imprinted microRNA gene cluster in placental development

• Project/Area Number: 16H04687
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Inoue Kimiko 国立研究開発法人理化学研究所, バイオリソース研究センター, 専任研究員 (70360500)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2017: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2016: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
• Keywords: 胎盤 / マイクロRNA / 刷り込み遺伝子 / ゲノム編集 / 発生・分化 / 発現制御 / ゲノム / 発生工学

Outline of Final Research Achievements

Genomic imprinting in mammals is an epigenetic process where the two parental alleles of a gene expressed exclusively. The parent of origin-specific monoallelic expression of imprinted genes is marked during their germline development. In some cases, multiple consecutive microRNA (miRNA) genes are encoded within the imprinted gene, and these genes are called miRNA clusters. In the mouse, the Sfmbt2 gene, an essential imprinted gene for placental development, contains the largest cluster of miRNAs in the mouse genome. However, its function during development remains to be elucidated. In this study, we investigated the role of this largest miRNA cluster in mouse development.

Academic Significance and Societal Importance of the Research Achievements

胎盤は、妊娠期間中に母体と胎児を結び栄養やガス交換を行う哺乳類特有の器官である。胎盤は母体の健康と胎児の成長に重要な役割を持っているが、胎盤形成に関与している遺伝子については未解明な点が多い。マイクロRNA（miRNA）はタンパクをコードせずに、他の遺伝子の発現を抑制する機能を持つ小さなRNAである。本研究では、刷り込み遺伝子内部に連続して存在するmiRNA遺伝子が、胎盤の正常な形成に重要な役割を占めることを明らかにしており、将来的には臨床における胎盤異常の原因解明やマーカー遺伝子の開発などに役立つと期待される。

Research Products

• [Journal Article] Loss of H3K27me3 imprinting in the Sfmbt2 miRNA cluster causes enlargement of cloned mouse placentas (2020)
  • Author(s): Inoue Kimiko、Ogonuki Narumi、Kamimura Satoshi、Inoue Hiroki、Matoba Shogo、Hirose Michiko、Honda Arata、Miura Kento、Hada Masashi、Hasegawa Ayumi、Watanabe Naomi、Dodo Yukiko、Mochida Keiji、Ogura Atsuo
  • Journal Title: Nature Communications Volume: 11 Issue: 1 Pages: 2150-2150
  • DOI: 10.1038/s41467-020-16044-8
  • Peer Reviewed / Open Access
• [Journal Article] Acrosin is essential for sperm penetration through the zona pellucida in hamsters (2020)
  • Author(s): Hirose Michiko、Honda Arata、Fulka Helena、Tamura-Nakano Miwa、Matoba Shogo、Tomishima Toshiko、Mochida Keiji、Hasegawa Ayumi、Nagashima Kiyoshi、Inoue Kimiko、Ohtsuka Masato、Baba Tadashi、Yanagimachi Ryuzo、Ogura Atsuo
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 117 Issue: 5 Pages: 2513-2518
  • DOI: 10.1073/pnas.1917595117
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Early production of offspring by <i>in vitro</i> fertilization using first-wave spermatozoa from prepubertal male mice (2019)
  • Author(s): MOCHIDA Keiji、HASEGAWA Ayumi、OGONUKI Narumi、INOUE Kimiko、OGURA Atsuo
  • Journal Title: Journal of Reproduction and Development Volume: 65 Issue: 5 Pages: 467-473
  • DOI: 10.1262/jrd.2019-042
  • NAID: 130007732105
  • Peer Reviewed / Open Access
• [Journal Article] Telomere shortening by transgenrational transmission of TNF-α-induced TERRA via ATF7 (2019)
  • Author(s): Binbin L, Maekawa T, Yoshida K, Ly N, Inoue K, Hasegawa A, Chatton B, Ogura A, Ishii S.
  • Journal Title: Nuc Acid Res Volume: 47 Issue: 1 Pages: 283-298
  • DOI: 10.1093/nar/gky1149
  • Peer Reviewed
• [Journal Article] Somatic Cell Nuclear Transfer in Mice: Basic Protocol and Its Modification for Correcting X Chromosome Inactivation Status (2018)
  • Author(s): Inoue Kimiko、Matoba Shogo、Ogura Atsuo
  • Journal Title: Methods Mol Biol. Volume: 1861 Pages: 55-65
  • DOI: 10.1007/978-1-4939-8766-5_5
  • ISBN: 9781493987658, 9781493987665
  • Peer Reviewed
• [Journal Article] Aberrant imprinting in mouse trophoblast stem cells established from somatic cell nuclear transfer-derived embryos (2018)
  • Author(s): Hirose Michiko、Hada Masashi、Kamimura Satoshi、Matoba Shogo、Honda Arata、Motomura Kaori、Ogonuki Narumi、Shawki Hossam H.、Inoue Kimiko、Takahashi Satoru、Ogura Atsuo
  • Journal Title: Epigenetics Volume: 13 Issue: 7 Pages: 693-703
  • DOI: 10.1080/15592294.2018.1507199
  • Peer Reviewed
• [Journal Article] Loss of H3K27me3 Imprinting in Somatic Cell Nuclear Transfer Embryos Disrupts Post-Implantation Development (2018)
  • Author(s): Matoba Shogo、Wang Huihan、Jiang Lan、Lu Falong、Iwabuchi Kumiko A.、Wu Xiaoji、Inoue Kimiko、Yang Lin、Press William、Lee Jeannie T.、Ogura Atsuo、Shen Li、Zhang Yi
  • Journal Title: Cell Stem Cell Volume: 23 Issue: 3 Pages: 343-354
  • DOI: 10.1016/j.stem.2018.06.008
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Identification of quantitative trait loci associated with the susceptibility of mouse spermatozoa to cryopreservation (2018)
  • Author(s): Liu J, Mochida K, Hasegawa A, Inoue K, Ogura A.
  • Journal Title: Journal of Reproduction and Development Volume: 64 Issue: 2 Pages: 117-127
  • DOI: 10.1262/jrd.2017-148
  • NAID: 130006699699
  • ISSN: 0916-8818, 1348-4400
  • Peer Reviewed / Open Access
• [Journal Article] Efficient and scheduled production of pseudopregnant female mice for embryo transfer by estrous cycle synchronization (2017)
  • Author(s): Hasegawa A, Mochida K, Ogonuki N, Hirose M, Tomishima T, Inoue K, Ogura A.
  • Journal Title: Journal of Reproduction and Development Volume: 63 Issue: 6 Pages: 539-545
  • DOI: 10.1262/jrd.2017-068
  • NAID: 130006250262
  • ISSN: 0916-8818, 1348-4400
  • Peer Reviewed / Open Access
• [Journal Article] Histone H3 Methylated at Arginine 17 Is Essential for Reprogramming the Paternal Genome in Zygotes. (2017)
  • Author(s): Hatanaka Y, Tsusaka T, Shimizu N, Morita K, Suzuki T, Machida S, Satoh M, Honda A, Hirose M, Kamimura S, Ogonuki N, Nakamura T, Inoue K, Hosoi Y, Dohmae N, Nakano T, Kurumizaka H, Matsumoto K, Shinkai Y, Ogura A.
  • Journal Title: Cell Rep Volume: 20(12) Issue: 12 Pages: 2756-2765
  • DOI: 10.1016/j.celrep.2017.08.088
  • Peer Reviewed / Open Access
• [Journal Article] The rodent-specific microRNA cluster within the Sfmbt2 gene is imprinted and essential for placental development. (2017)
  • Author(s): Inoue K, Hirose M, Inoue H, Hatanaka Y, Honda A, Hasegawa A, Mochida K, Ogura A.
  • Journal Title: Cell Reports、印刷中 Volume: -
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Hyper-reactive cloned mice generated by direct nuclear transfer of antigen-specific CD4+ T cells. (2017)
  • Author(s): Kaminuma O, Katayama K, Inoue K, Saeki M, Nishimura T, Kitamura N, Shimo Y, Tofukuji S, Ishida S, Ogonuki N, Kamimura S, Oikawa M, Katoh S, Mori A, Shichijo M, Hiroi T, Ogura A.
  • Journal Title: EMBO Reports、印刷中 Volume: -
  • Peer Reviewed / Open Access
• [Journal Article] CRISPR/Cas9-mediated genome editing in wild-derived mice: generation of tamed wild-derived strains by mutation of the a (nonagouti) gene (2017)
  • Author(s): Michiko Hirose, Ayumi Hasegawa, Keiji Mochida, Shogo Matoba, Yuki Hatanaka, Kimiko Inoue, Tatsuhiko Goto, Hideki Kaneda, Ikuko Yamada, Tamio Furuse, Kuniya Abe, Yoshihisa Uenoyama, Hiroko Tsukamura, Shigeharu Wakana, Arata Honda, and Atsuo Ogura
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 42476-42476
  • DOI: 10.1038/srep42476
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mouse D1Pas1, a DEAD-box RNA helicase, is required for the completion of first meiotic prophase in male germ cells (2016)
  • Author(s): Inoue H, Ogonuki N, Hirose M, Hatanaka Y, Matoba S, Chuma S, Kobayashi K, Wakana S, Noguchi J, Inoue K, Tanemura K, *Ogura A
  • Journal Title: Biochem Biophys Res Commun Volume: 478 Issue: 2 Pages: 592-8
  • DOI: 10.1016/j.bbrc.2016.07.109
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 胎盤特異的インプリント遺伝子Sfmbt2内のマイクロRNAクラスターのインプリント消失は体細胞クローンマウスの胎盤異常を引き起こす (2019)
  • Author(s): 井上 貴美子, 越後貫 成美, 上村 悟氏, 井上 弘貴, 的場 章悟, 廣瀬 美智子, 本多 新, 三浦 健人, 羽田 政司, 百々 由希子, 長谷川 歩未, 持田 慶司, 小倉 淳郎
  • Organizer: 日本繁殖生物学会
• [Presentation] クローンマウスの胎盤過形成はSfmbt2 miRNAクラスターのインプリント消失により引き起こされる (2019)
  • Author(s): 井上貴美子，越後貫成美，上村悟氏，井上弘貴，的場章悟，廣瀬美智子，三浦健人，羽田政司，百々由希子，長谷川歩未，持田慶司，小倉淳郎
  • Organizer: 日本実験動物学会
• [Presentation] 胎盤特異的な父性発現遺伝子Sfmbt2の欠損マウス個体における表現型の解析 (2018)
  • Author(s): 井上貴美子、廣瀬美智子、長谷川歩未、持田慶司、小倉淳郎
  • Organizer: 日本実験動物学会
• [Presentation] 胎盤特異的な父性発現遺伝子Sfmbt2の欠損マウス個体における表現型の解析 (2018)
  • Author(s): 井上貴美子、廣瀬美智子、長谷川歩未、持田慶司、小倉淳郎
  • Organizer: 日本繁殖生物学会
• [Presentation] The rodent-specific microRNA cluster within the Sfmbt2 gene is imprinted and essential for placental development (2017)
  • Author(s): Kimiko Inoue, Michiko Hirose, Hiroki Inoue, Yuki Hatanaka, Arata Honda, Ayumi Hasegawa, Keiji Mochida, Atsuo Ogura
  • Organizer: Epigeneticsシンポジウム2017
  • Place of Presentation: 茨城県、つくば市
  • Year and Date: 2017-02-16
• [Presentation] 抗原特異的CD4陽性T細胞由来の核移植クローンマウス作製 (2017)
  • Author(s): 井上貴美子、神沼修、越後貫成美、上村悟氏、及川真実、的場章悟、廣井隆親、小倉淳郎
  • Organizer: 第64回実験動物学会
• [Presentation] The rodent-specific microRNA cluster within the Sfmbt2 gene is imprinted and essential for placental development (2017)
  • Author(s): Kimiko Inoue, Michiko Hirose, Hiroki Inoue, Yuki Hatanaka, Arata Honda, Ayumi Hasegawa, Keiji Mochida, Atsuo Ogura
  • Organizer: 4th World Congress of Reproductive Biology 2017
  • Int'l Joint Research
• [Presentation] バイオリソースセンターにおける実験動物の生殖工学技術の開発 (2017)
  • Author(s): 井上 貴美子、 長谷川 歩未、 持田 慶司、小倉 淳郎
  • Organizer: Cryoconference2017
  • Invited
• [Remarks] 遺伝工学基盤技術室HP
  • URL: http://ja.brc.riken.jp/lab/kougaku/index.html
• [Remarks] 体細胞クローンマウスの胎盤異常の原因を解明
  • URL: https://www.riken.jp/press/2020/20200501_2/index.html
• [Remarks] 遺伝工学基盤技術室ホームページ
  • URL: https://ja.brc.riken.jp/lab/kougaku/index.html
• [Remarks] 遺伝工学基盤技術室ホームページ
  • URL: http://ja.brc.riken.jp/lab/kougaku/index.html