Study for defining totipotency mechanism of oocytes

• Project/Area Number: 25670710
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: National Center for Child Health and Development
• Principal Investigator: Akutsu Hidenori 国立研究開発法人国立成育医療研究センター, 生殖医療研究部, 部長 (50347225)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: 発生 / 卵子 / 全能性 / 核タンパク質 / 受精卵 / マイクロアレイ

Outline of Final Research Achievements

Spatiotemporal expression of transcription factors is crucial for genomic reprogramming processes in both in vivo and in vitro. Cellular reprogramming and differentiation are accompanied by dynamic transcriptional changes and transcription factors play central roles in both processes. Dramatic alterations of cellular fates occur during preimplantation embryo development. In mice, after fertilization, an important transcription factor responsible for sustaining pluripotency is the Pou5f1 protein (also known as Oct4). Our deep expression analysis and dose-dependent functional analyses in the preimplantation stages were conducted to address the in vivo Oct4 potential for developmental reprogramming. Our recent findings provide new insight into a role for Oct4 in epigenetic reprogramming toward totipotency in vivo. The spatiotemporal regulation and fine tuning of Oct4 is essential for cellular reprogramming and integrity.

Research Products

• [Journal Article] Imbalance between the expression dosages of X-chromosome and autosomal genes in mammalian oocytes (2015)
  • Author(s): Atsushi Fukuda, Motohiko Tanino, Ryo Matoba, Akihiro Umezawa, Hidenori Akutsu
  • Journal Title: Scientific reports Volume: 5 Issue: 1 Pages: 14101-14101
  • DOI: 10.1038/srep14101
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Generation of primitive neural stem cells from human fibroblasts using a defined set of factors. (2015)
  • Author(s): 3.Miura T, Sugawara T, Fukuda A, Machida M, Tamoto R, Kawasaki T, Umezawa A, Akutsu H.
  • Journal Title: Biology Open Volume: 4 Issue: 11 Pages: 1595-1607
  • DOI: 10.1242/bio.013151
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Ethical acceptability of research on human-animal chimeric embryos: summary of opinions by the Japanese Expert Panel on Bioethics (2015)
  • Author(s): Mizuno H, Akutsu H, Kato K
  • Journal Title: Life Sci Soc Policy. Volume: 11 Issue: 1 Pages: 15-15
  • DOI: 10.1186/s40504-015-0033-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Chromatin condensation of Xist genomic loci during oogenesis in mice (2015)
  • Author(s): Fukuda, A., Mitani, A., Miyashita, T., Umezawa, A., Akutsu, H
  • Journal Title: Development Volume: 142 Pages: 4049-4055
  • DOI: 10.1242/dev.127308
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Notch inhibition allows oncogene-independent generation of iPS cells (2015)
  • Author(s): Ichida JK, T C W J, Williams LA, Carter AC, Shi Y, Moura MT, Ziller M, Singh S, Amabile G, Bock C, Umezawa A, Rubin LL, Bradner JE, Akutsu H, Meissner A, Eggan K
  • Journal Title: Nature Chemical Biology Volume: 1 Issue: 8 Pages: 632-639
  • DOI: 10.1038/nchembio.1552
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The role of maternal-specific H3K9me3 modification in establishing imprinted X-chromosome inactivation and embryogenesis in mice. (2014)
  • Author(s): Fukuda A, Tomikawa J, Miura T, Hata K, Nakabayashi K, Eggan K, Akutsu H, Umezawa A.
  • Journal Title: Nat Commun. Volume: 5 Issue: 1 Pages: 5464-5464
  • DOI: 10.1038/ncomms6464
  • Peer Reviewed / Open Access
• [Presentation] The role of asymmetric histone modifications in embryo development (2015)
  • Author(s): Akutsu, Hidenori
  • Organizer: IFFS/JSRM International Meeting 2015
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2015-04-26
  • Int'l Joint Research / Invited
• [Presentation] 卵子老化機序解明に向けたES細胞の応用 (2014)
  • Author(s): 阿久津英憲
  • Organizer: 第32回日本受精着床学会総会・学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2014-07-31 – 2014-08-01
  • Invited