Basic study to explore molecular mechanism of the oocyte effecting on developmental potential

• Project/Area Number: 21390456
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: National Research Institute for Child Health and Development
• Principal Investigator: AKUTSU Hidenori 独立行政法人国立成育医療研究センター, 生殖・細胞医療研究部, 室長 (50347225)
• Co-Investigator(Kenkyū-buntansha): HAMATANI Toshio 慶應大学, 医学部, 講師 (60265882) ; 豊田 雅士 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 研究所老年病研究チーム, 研究副部長 (50392486) ; 名取 道也 独立行政法人国立成育医療研究センター, 所長 (80101913)
• Co-Investigator(Renkei-kenkyūsha): TOYODA Masashi 東京都健康長寿医療センター, 研究所, 部長 (50392486)
• Project Period (FY): 2009-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2013: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2011: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2010: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2009: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: ES細胞 / 卵細胞 / 幹細胞 / 胚細胞腫瘍 / 網羅的遺伝子発現解析 / 卵子加齢 / 老化 / 若返り

Research Abstract

We analyzed embryonic stem (ES) cells derived from aging mice model. It was found that some genes of Wnt-beta-Catenin signaling were relatively lower expression compared with control ES cells. Then, we successfully derived ES-like cells from beta-Catenin defected embryos. The ES cells showed severely impaired in pluripotential differentiation under loss of Beta-Catenin, although can maintain self-renewal ability. Additionally, we found mixed germ cell tumor was generated from the beta-Catenin defected cells in vivo. Taken together, beta-Catenin functions pleiotropically in differentiation and tumorigenesis in mouse embryo derived stem cells.

Research Products

• [Journal Article] ヒトES/iPS細胞と生殖補助医療 (2014)
  • Author(s): 阿久津英憲
  • Journal Title: 産科と婦人科 Volume: 3 Pages: 295-302
• [Journal Article] β-Catenin Functions Pleiotropically in Differentiation and Tumorigenesis in Mouse Embryo-Derived Stem Cells (2013)
  • Author(s): Okumura N, Akutsu H, Sugawara T, Miura T, Takezawa Y, Hosoda A, Yoshida K, Ichida JK, Yamada M, Hamatani T, Kuji N, Miyado K, Yoshimura Y, Umezawa A
  • Journal Title: PLoS One Volume: 8
• [Journal Article] Age-associated telomere shortening in mouse oocytes (2013)
  • Author(s): Yamada-Fukunaga T, Yamada M, Hamatani T, Chikazawa N, Ogawa S, Akutsu H, Miura T, Miyado K, Tarín JJ, Kuji N, Umezawa A, Yoshimura Y
  • Journal Title: Reprod Biol Endocrinol Volume: 11 Pages: 108-108
• [Journal Article] β-catenin functions pleiotropically in differentiation and tumorigenesis in mouse embryo-derived stem cells (2013)
  • Author(s): Okumura N, Akutsu H, Sugawara T, Miura T, Takezawa Y, Hosoda A, Yoshida K, Ichida JK, Yamada M, Hamatani T, Kuji N, Miyado K, Yoshimura Y, Umezawa A
  • Journal Title: PLoS One Volume: 8(5) Issue: 5 Pages: 63265-63265
  • DOI: 10.1371/journal.pone.0063265
  • Peer Reviewed
• [Journal Article] Age-associated telomere shortening in mouse oocytes (2013)
  • Author(s): Yamada-Fukunaga T, Yamada M, Hamatani T, Chikazawa N, Ogawa S, Akutsu H, Miura T, Miyado K, Tarin JJ, Kuji N, Umezawa A, Yoshimura Y
  • Journal Title: Reprod Biol Endocrinol Volume: 11 Issue: 1 Pages: 108-108
  • DOI: 10.1186/1477-7827-11-108
  • Peer Reviewed
• [Journal Article] ES細胞-その基礎と臨床応用に向けた展望- (2013)
  • Author(s): 阿久津英憲
  • Journal Title: 整形・災害外科（再生医療の現況と最前線） Volume: 56 Pages: 501-506
• [Journal Article] A medium-chain fatty acid as an alternative energy source in mouse preimplantation development (2012)
  • Author(s): Yamada M, Takanashi K, Hamatani T, Hirayama A, Akutsu H, Fukunaga T, Ogawa S, Sugawara K, Shinoda K, Soga T, Umezawa A, Kuji N, Yoshimura Y, Tomita M
  • Journal Title: Scientific Reports Volume: 2 Pages: 980-980
• [Journal Article] Investigating cellular identity and manipulating cell fate using induced pluripotent stem cells (2012)
  • Author(s): Sugawara T, Nishino K, Umezawa A, Akutsu H
  • Journal Title: Stem Cell Res Ther Volume: 3 Pages: 8-8
• [Journal Article] Human spermatozoal RNAs (2012)
  • Author(s): Hamatani T
  • Journal Title: Fertil Steril Volume: 97 Pages: 275-281
• [Journal Article] A medium-chain fatty acid as an alternative energy source in mouse preimplantation development. (2012)
  • Author(s): Yamada M
  • Journal Title: Science Reports Volume: 2 Issue: 1 Pages: 930-930
  • DOI: 10.1038/srep00930
  • Peer Reviewed
• [Journal Article] Aging of the Female Reproductive System (2011)
  • Author(s): Egli D, Akutsu H
  • Journal Title: J Mamm Ova Res Volume: 28 Pages: 118-125
  • NAID: 10029898437
• [Journal Article] Beta-catenin is a molecular switch that regulates transition of cell-cell adhesion to fusion (2011)
  • Author(s): Takezawa Y, Yoshida K, Miyado K, Sato M, Nakamura A, Kawano N, Sakakibara K, Kondo T, Harada Y, Ohnami N, Kanai S, Miyado M, Saito H, Takahashi Y, Akutsu H, Umezawa A
  • Journal Title: Scientific Reports Volume: 1 Pages: 68-68
• [Journal Article] Spermatozoal RNA profiling towards a clinical evaluation of sperm quality (2011)
  • Author(s): Hamatani T
  • Journal Title: Reprod Biomed Online Volume: 22 Pages: 103-105
• [Journal Article] ARTによる出生時の問題児のエピジェネティックス異常との関連 (2011)
  • Author(s): 阿久津英憲, 佐藤俊, 秦健一郎
  • Journal Title: 臨床婦人科産科 Volume: 65 Pages: 770-776
• [Journal Article] ヒトES 細胞, iPS細胞」生命の誕生に向けて(第二版)編集 (2011)
  • Author(s): 阿久津英憲, 佐藤星子
  • Journal Title: 日本哺乳類動物卵子学会 Pages: 268-272
• [Journal Article] Involvement of a novel preimplantation-specific gene encoding the high mobility group box protein Hmgpi in early embryonic development (2010)
  • Author(s): Yamada M, Hamatani T, Akutsu H, Chikazawa N, Kuji N, Yoshimura Y, Umezawa A
  • Journal Title: Hum Mol Genet Volume: 19 Pages: 480-493
• [Journal Article] Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells (2010)
  • Author(s): Stadtfeld M, Apostolou E, Akutsu H, Fukuda A, Follett P, Natesan S, Kono T, Shioda T, Hochedlinger K
  • Journal Title: Nature Volume: 465 Pages: 175-181
• [Journal Article] Acute stress may induce ovulation in women (2010)
  • Author(s): Tarín JJ, Hamatani T, Cano A
  • Journal Title: Reprod Biol Endocrinol Volume: 8 Pages: 53-53
• [Journal Article] Defining cell identity by comprehensive gene expression profiling (2010)
  • Author(s): Toyoda M, Hamatani T, Okada H, Matsumoto K, Saito H, Umezawa A
  • Journal Title: Curr Med Chem Volume: 17 Pages: 3245-3252
• [Journal Article] Defining hypo-methylated regions of stem cell-specific promoters in human iPS cells derived from extra-embryonic amnions and lung fibroblasts. (2010)
  • Author(s): Nishino K, Toyoda M, Yamazaki-Inoue M, Makino H, Fukawatase Y, Chikazawa E, Takahashi Y, Miyagawa Y, Okita H, Kiyokawa N, Akutsu H, Umezawa A.
  • Journal Title: PLoS One. Volume: 5
  • Peer Reviewed
• [Journal Article] Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells. (2010)
  • Author(s): Stadtfeld M, Apostolou E, Akutsu H, Fukuda A, Follett P, Natesan S, Kono T, Shioda T, Hochedlinger K.
  • Journal Title: Nature Volume: 465 Pages: 175-181
  • Peer Reviewed
• [Journal Article] A small-molecule inhibitor of tgf-Beta signaling replaces sox2 in reprogramming by inducing nanog (2009)
  • Author(s): Ichida JK, Blanchard J, Lam K, Son EY, Chung JE, Egli D, Loh KM, Carter AC, Di Giorgio FP, Koszka K, Huangfu D, Akutsu H, Liu DR, Rubin LL, Eggan K
  • Journal Title: Cell Stem Cell Volume: 5 Pages: 491-503
• [Journal Article] Fitz-Gerald F, Zhang K, Melton D, Eggan K. Optimal timing of inner cell mass isolation increases the efficiency of human embryonic stem cell derivation and allows generation of sibling cell lines (2009)
  • Author(s): Chen A, Egli D, Niakan K, Deng J, Akutsu H, Yamaki M, Chad C
  • Journal Title: Cell Stem Cell Volume: 4 Pages: 103-106
• [Journal Article] Maintenance of pluripotency and self-renewal ability of mouse embryonic stem cells in the absence of tetraspanin CD9 (2009)
  • Author(s): Akutsu H, Miura T, Machida M, Birumachi JI, Hamada A, Yamada M, Sullivan S, Miyado K, Umezawa A
  • Journal Title: Differentiation Volume: 78 Pages: 137-142
• [Journal Article] Involvement of a novel preimplantation-specific gene encoding the high mobility group box protein Hmgpi in early embryonic development (2009)
  • Author(s): Yamada M, Hamatani T, Akutsu H, Chikazawa N, Kuji N, Yoshimura Y, Umezawa A
  • Journal Title: Hum Mol Genet 19 Pages: 480-493
  • Peer Reviewed
• [Journal Article] A small-molecule inhibitor of tgf-Beta signaling replaces sox2 in reprogramming by inducing nanog (2009)
  • Author(s): Ichida JK, Blanchard J, Lam K, Son EY, Chung JE, Egli D, Loh KM, Carter AC, Di Giorgio FP, Koszka K, Huangfu D, Akutsu H, Liu DR, Rubin LL, Eggan K.
  • Journal Title: Cell Stem Cell. 5 Pages: 491-503
  • Peer Reviewed
• [Journal Article] Maintenance of pluripotency and self-renewal ability of mouse embryonic stem cells in the absence of tetraspanin CD9 (2009)
  • Author(s): Akutsu H, Miura T, Machida M, Birumachi J, Hamada A, Yamada M, Sullivan S, Miyado K, Umezawa A.
  • Journal Title: Differentiation 78 Pages: 137-142
  • Peer Reviewed
• [Presentation] Beta catenin functions pleiotropically in differentiation and tumorigenesis in mouse embryo-derived stem cells (poster) T-2375 (2013)
  • Author(s): Akutsu H, Sugawara T, Takezawa Y, Kawasaki T, Okumura N, Miura T, Miyado K, Umezawa A
  • Organizer: 11th ISSCR 2013 Annual Meeting
  • Place of Presentation: Boston, MA
• [Presentation] 着床前期胚において特異的に発現する新規SCAN-zinc finger 遺伝子Zfp371 の解析 (2013)
  • Author(s): 小川誠司, 浜谷敏生, 阿久津英憲, 山田満稔, 奥村典子, 菅原かな, 井上 治, 福永朝子, 梅澤明弘, 久慈直昭, 青木大輔, 吉村泰典
  • Organizer: 第65回日本産科婦人科学会学術講演会
  • Place of Presentation: 札幌
• [Presentation] β-カテニンは分化多能性に必須でありその機能不全は悪性胚細胞腫瘍発生に関与している (2013)
  • Author(s): 奥村典子, 阿久津英憲, 浜谷敏生, 山田満稔, 菅原かな, 小川誠司, 井上 治, 上條慎太郎, 梅澤明弘, 久慈直昭, 青木大輔, 吉村泰典
  • Organizer: 第65回日本産科婦人科学会学術講演会
  • Place of Presentation: 札幌
• [Presentation] 着床前期胚において特異的に発現する新規SCAN-zinc finger遺伝子Zfp371の解析 (2013)
  • Author(s): 小川誠司
  • Organizer: 第65回日本産科婦人科学会学術講演会
  • Place of Presentation: 札幌
• [Presentation] Beta catenin functions pleiotropically in differentiation and tumorigenesis in mouse embryo-derived stem cells (2013)
  • Author(s): Akutsu, Hidenori
  • Organizer: 11th ISSCR 2013 Annual Meeting
  • Place of Presentation: Boston, MA, US
• [Presentation] Human ES cells : aquired pluripotency from blastocysts (2012)
  • Author(s): Akutsu H
  • Organizer: Asia Pacific Initiative on Reproduction 2012
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2012-08-31
• [Presentation] Human ES cells: aquired pluripotency from blastocysts (2012)
  • Author(s): Akutsu H
  • Organizer: Asia Pacific Initiative on Reproduction 2012
  • Place of Presentation: Osak, Japan
  • Invited
• [Presentation] エピゲノムの基礎知識 (2011)
  • Author(s): 阿久津英憲
  • Organizer: エピゲノムワークショップ 第52回日本哺乳動物卵子学会
  • Place of Presentation: 大田原
  • Year and Date: 2011-05-21
• [Presentation] 受精からの発生で理解する幹細胞生物学 (2011)
  • Author(s): 阿久津英憲
  • Organizer: 日本生殖再生医学会第6回学術集会
  • Place of Presentation: 東京
  • Year and Date: 2011-03-13
• [Presentation] Xeno-free Growth and Expansion of Human Pluripotent Stem Cells (2010)
  • Author(s): Hidenori Akutsu
  • Organizer: The 23rd Annual and International Meeting of the Japanese Association for Animal Cell Technology
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 2010-09-03
• [Presentation] 臨床グレード幹細胞樹立の試み (2010)
  • Author(s): 阿久津英憲
  • Organizer: 第28回日本ヒト細胞学会学術集会
  • Place of Presentation: つくば市
  • Year and Date: 2010-08-28
• [Presentation] Xeno-Free Growth and Expansion of Human Pluripotent Stem Cells (2010)
  • Author(s): Hidenori Akutsu
  • Organizer: The 8^<th> ISSCR Annual Meeting
  • Place of Presentation: San Francisco, CA, USA
  • Year and Date: 2010-06-18
• [Presentation] 難治性疾患克服に向けたヒトiPS細胞の可能性 (2009)
  • Author(s): 阿久津英憲
  • Organizer: 日本人類遺伝学会第54回大会
  • Place of Presentation: 東京
• [Presentation] Human Embryonic stem cells and WS Cells : Potential tool for Low temperature medical experiments (2009)
  • Author(s): 阿久津英憲
  • Organizer: 第36回日本低温医学会総会・学術集会シンポジウム2
  • Place of Presentation: 東京