Molecular mechanisms regulating conversion of pluripotential stem cells into Germ cells

• Project/Area Number: 25650104
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Morphology/Structure
• Research Institution: Tohoku University
• Principal Investigator: Yasuhisa Matsui 東北大学, 加齢医学研究所, 教授 (40241575)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI KAZUYA 弘前大学, 農学生命科学部, 准教授 (50360110)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 多能性幹細胞 / 生殖細胞 / RNA干渉法 / プラナリア / ニワトリ / Max / Brg1

Outline of Final Research Achievements

We previously found that knock-down of transcription factors, Max and Brg1 in mouse embryonic stem cells (ESCs) by RNA interference (RNAi) resulted in global induction of germ cell-specific genes. In this study, we attempted to examine whether Max and Brg1 also play a similar role on pluripotential stem cells in diverse organisms such as chick and planaria. We found that Max- or Brg1-knockdown (KD) in mature planaria containing pluripotential neoblast cells resulted in up-regulation of some germ cell-specific genes. We also found increased expression of some germ cell-specific genes by Max-KD in pluripotential blastoderm cells derived from early chick embryos. The results indicate that Max and Brg1 are involved in repression of germ cell-specific genes in planaria and chick, but they repress only a part of germ cell-specific genes. Therefore functions of Max and Brg1 may be somewhat different among mouse ESCs, planaria and chick pluripotential stem cells.

Research Products

• [Journal Article] The protein phosphatase 6 catalytic subunit (Ppp6c) is indispensable for proper post-implantation embryogenesis. (2016)
  • Author(s): Ogoh, H., Tanuma, N., Matsui, Y., Hayakawa, N., Inagaki, A., Sumiyoshi, M., Momoi, Y., Kishimoto, A., Suzuki, M., Sasaki, N., Ohuchi, T., Nomura, M., Teruya, Y., Yasuda, K., Watanabe, T., Shima, H.
  • Journal Title: Mechanisms of Development Volume: 139 Pages: 1-9
  • DOI: 10.1016/j.mod.2016.02.001
  • Peer Reviewed / Open Access
• [Journal Article] Max as a biological blockade that restricts meiotic process in ESCs. (2016)
  • Author(s): Suzuki A, Hirasaki M, Hishida T, Okamura D, Wu J, Ueda A, Nishimoto M, Nakachi Y, Mizuno Y, Okazaki Y, Matsui Y, *Izpisua Belmonte JC, Okuda A.
  • Journal Title: Nat Commun Volume: 7 Issue: 1 Pages: 11056-11056
  • DOI: 10.1038/ncomms11056
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sall4 is essential for mouse primordial germ cell specification by suppressing somatic cell program genes. (2015)
  • Author(s): Yamaguchi YL, Tanaka SS, Kumagai M, Fujimoto Y, Terabayashi T, Matsui Y, Nishinakamura R.
  • Journal Title: Stem Cells. Volume: 33(1) Issue: 1 Pages: 289-300
  • DOI: 10.1002/stem.1853
  • Peer Reviewed / Open Access
• [Journal Article] Novel sex-dependent differentially methylated regions are demethylated in adult male mouse livers (2015)
  • Author(s): Ito S, Hirabayashi K, Moriishi K, Matsui Y, Moriya K, Koike K, Matsuura Y, Shiota K, Yagi S.
  • Journal Title: Biochem Biophys Res Commun Volume: 462 Issue: 4 Pages: 332-338
  • DOI: 10.1016/j.bbrc.2015.04.137
  • Peer Reviewed
• [Journal Article] Mice doubly-deficient in the Arf GAPs SMAP1 and SMAP2 exhibit embryonic lethality (2015)
  • Author(s): Sumiyoshi M, Rai S, Tanaka H, Matsumura I, et al.
  • Journal Title: FEBS Lett. Volume: 589 Issue: 19PartB Pages: 2754-2762
  • DOI: 10.1016/j.febslet.2015.07.050
  • Peer Reviewed / Open Access
• [Journal Article] Sex Specification and Heterogeneity of Primordial Germ Cells in Mice. (2015)
  • Author(s): Sakashita, A., Kawabata, Y., Jincho, Y., Tajima, S., Kumamoto, S., Kobayashi, H., Matsui, Y. and Kono, T.
  • Journal Title: PLoS ONE Volume: 10 Issue: 12 Pages: 1-21
  • DOI: 10.1371/journal.pone.0144836
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The majority of early primordial germ cells acquire pluripotency by Akt activation. (2014)
  • Author(s): Matsui Y et al.
  • Journal Title: Development Volume: 141 Issue: 23 Pages: 4457-4467
  • DOI: 10.1242/dev.113779
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The ADP-ribosylation factor 1 gene is indispensable for mouse embryonic development after implantation. (2014)
  • Author(s): Hayakawa, N., Ogoh, H., Sumiyoshi, M., Matsui, Y., Nishikawa, S., Miyamoto, K., Maede, Y., Kiyonari, H., Suzuki, M. and Watanabe, T.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 453 Issue: 4 Pages: 748-753
  • DOI: 10.1016/j.bbrc.2014.10.014
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 始原生殖細胞の分化と多能性幹細胞への再プログラム化のメカニズム (2014)
  • Author(s): 松居靖久
  • Journal Title: 生化学 Volume: 86 Pages: 726-734
  • NAID: 40020314078
  • Peer Reviewed
• [Journal Article] Planarian D-amino acid oxidase is involved in ovarian development during sexual induction. (2014)
  • Author(s): Maezawa T, Tanaka H, Nakagawa H, Ono M, Aoki M, Matsumoto M, Ishida T, Horiike K, Kobayashi K.
  • Journal Title: Mech of Development Volume: 132 Pages: 69-78
  • DOI: 10.1016/j.mod.2013.12.003
  • Peer Reviewed / Open Access
• [Journal Article] A current view of the epigenome in mouse primordial germ cells. (2014)
  • Author(s): Matsui, Y. and Mochizuki, K.
  • Journal Title: Molecular Reproduction and Development Volume: 81 Issue: 2 Pages: 160-170
  • DOI: 10.1002/mrd.22214
  • Peer Reviewed
• [Journal Article] On the fate of primordial germ cells injected into early mouse embryos. (2013)
  • Author(s): Leitch, H.G., Okamura, D., Durcova-Hills, G., Stewart, C.L., Gardner, R.L., Matsui, Y., Papaioannou, V.E.
  • Journal Title: Developmental Biology Volume: 385 Issue: 2 Pages: 155-159
  • DOI: 10.1016/j.ydbio.2013.11.014
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] An RNAi screen for histone modifier genes involved in development of primordial germ cells in mice (2016)
  • Author(s): K. Mochizuki, H. Yokoyama and Y. Matsui.
  • Organizer: KEYSTONE SYMPOSIA on Molecular and Cellular Biology
  • Place of Presentation: British Columbia, Canada
  • Year and Date: 2016-03-20
  • Int'l Joint Research
• [Presentation] マウス胎仔線維芽細胞から始原生殖細胞を直接誘導する試み (2015)
  • Author(s): 関中 保、野瀬俊明、松居靖久
  • Organizer: 第３８回日本分子生物学会年会・第８８回日本生化学会大会・合同大会
  • Place of Presentation: 神戸、神戸ポートアイランド
  • Year and Date: 2015-12-03
• [Presentation] Identification and characterization of mouse cancer/tesits aitigen genes. (2015)
  • Author(s): Nana Aoki, Kentaro Mochizuki, Yasuhisa Matsui
  • Organizer: 第３８回日本分子生物学会年会・第８８回日本生化学会大会・合同大会
  • Place of Presentation: 神戸、神戸ポートアイランド
  • Year and Date: 2015-12-02
• [Presentation] Dnd1変異マウスの始原生殖細胞におけるヒストン修飾解析 (2015)
  • Author(s): 顧巍、望月研太郎、松居靖久
  • Organizer: 第３８回日本分子生物学会年会・第８８回日本生化学会大会・合同大会
  • Place of Presentation: 神戸、神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] ナイーブ型多能性幹細胞を生殖細胞に直接変換する試み (2015)
  • Author(s): 松居靖久
  • Organizer: 第108回日本繁殖生物学会大会
  • Place of Presentation: 宮崎、宮崎大学
  • Year and Date: 2015-09-28
  • Invited
• [Presentation] Analysis of the machanisms that promote the reprogramming in Akt-acivated rimordial germ cells. (2015)
  • Author(s): Asuka Takehara, Yuko Tokitake, Yasuhisa Mastui.
  • Organizer: 48th Annual Meeting of the Japanese Society of Developmental Biologists
  • Place of Presentation: 筑波、つくば国際会議場
  • Year and Date: 2015-06-02
• [Presentation] An attempt of direct reprogramming of mouse embryonic fibroblasts into primordial germ cells. (2015)
  • Author(s): Tamotsu Sekinaka, Toshiaki Noce, Yasuhisa Matsui
  • Organizer: 48th Annual Meeting of the Japanese Society of Developmental Biologists
  • Place of Presentation: 筑波、つくば国際会議場
  • Year and Date: 2015-06-02
• [Presentation] An RNAi screen for histone modifier genes involved in primordial germ cell fate determination in mice. (2015)
  • Author(s): Kentaro Mochizuki, Yasuhisa Matsui
  • Organizer: 48th Annual Meeting of the Japanese Society of Developmental Biologists
  • Place of Presentation: 筑波、つくば国際会議場
  • Year and Date: 2015-06-02
• [Presentation] 始原生殖細胞の分化と再プログラム化の分子機構 (2015)
  • Author(s): 松居靖久
  • Organizer: 第60回日本生殖医学会学術講演会
  • Place of Presentation: 横浜、パシフィコ横浜
  • Year and Date: 2015-04-27
  • Invited
• [Presentation] 胚性幹細胞の始原生殖細胞へのin vitro直接誘導に必要な因子の同定 (2014)
  • Author(s): 林 陽平、前田郁麻、松居靖久
  • Organizer: ３７回 日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-25
  • Invited
• [Presentation] 生殖細胞性と細胞分化多能性の制御機構 (2014)
  • Author(s): 松居靖久
  • Organizer: 学際ライフサイエンスシンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2014-10-31
  • Invited
• [Presentation] プラナリアの生殖様式転換機構：有性化因子による無性生殖から有性生殖への誘導について (2014)
  • Author(s): 小林一也
  • Organizer: 第６０回日本寄生虫学会・日本衛生動物学会北日本支部合同大会
  • Place of Presentation: 盛岡
  • Year and Date: 2014-10-18
  • Invited
• [Presentation] 多能性幹細胞と生殖細胞を隔てるエピジェネティック障壁 (2014)
  • Author(s): 松居靖久
  • Organizer: 日本遺伝学会第86回大会
  • Place of Presentation: 長浜
  • Year and Date: 2014-09-19
  • Invited
• [Presentation] プラナリア生殖器官特異的に発現するアミノ酸輸送体ホモログの解析 (2014)
  • Author(s): 石川正樹・前澤孝信・小林一也
  • Organizer: 日本動物学会第８５回仙台大会
  • Place of Presentation: 仙台
  • Year and Date: 2014-09-13
• [Presentation] 新奇プラナリア卵黄タンパク質について (2014)
  • Author(s): 川瀬 摂・岩谷 尚・田中裕之・坂元君年・小林一也
  • Organizer: 日本動物学会第８５回仙台大会
  • Place of Presentation: 仙台
  • Year and Date: 2014-09-13
• [Presentation] 川に、陸に、身近にウヨウヨしているプラナリアを観察してみよう (2014)
  • Author(s): 岡本 光・柳原由実・石川正樹・小林一也・中村剛之
  • Organizer: 日本動物学会第８５回仙台大会（動物学ひろば）
  • Place of Presentation: 仙台
  • Year and Date: 2014-09-13
• [Presentation] ラナリア生殖器官分化に注目したß-カテニン遺伝子の機能解析 (2014)
  • Author(s): 前澤孝信・菊池康哉・織井秀文・小林一也
  • Organizer: 日本動物学会第８５回仙台大会
  • Place of Presentation: 仙台
  • Year and Date: 2014-09-11
• [Presentation] プラナリア生殖器官形成に注目したFGFR関連遺伝子の機能解析 (2014)
  • Author(s): 柳原由実・中川晴香・前澤孝信・梅園良彦・阿形清和・小林一也
  • Organizer: 日本動物学会第８５回仙台大会
  • Place of Presentation: 仙台
  • Year and Date: 2014-09-11
• [Presentation] Tryptophan enhances the reproductive organs-specific expression level of an amino acid transporter homolog, Dr-slc38A9 in the sexual worms of Dugesia ryukyuensis. (2014)
  • Author(s): Ishikawa, M, Maezawa, T., Kobayashi, K
  • Organizer: The 1st Asian PlanNet Meeting
  • Place of Presentation: Hong Kong
  • Year and Date: 2014-05-09