potency and safety of iPS cells using preimplantation embryo specific genes

• Project/Area Number: 26462477
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: The University of Tokyo
• Principal Investigator: HIRATA TETSUYA 東京大学, 医学部附属病院, 講師 (30431860)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: iPS / 着床前期胚 / potency / Zscan4 / iPS細胞 / ES細胞

Outline of Final Research Achievements

It is not an oncogene like c-Myc but a new iPS inducer expressed in preimplantation embryo is important for safety. Zscan4 is one of the genes specific to the 2 cell stage in which embryonic genes are activated. We showed that by using this Zscan 4, the production efficiency of murine iPS cells greatly improves in a short period of time. In this study, we conducted research to obtain stable, high-quality iPS cells that can be clinically applied using iPS cells prepared with this Zscan4. Introduction of Zscan4ERT2 into ES cells increased the frequency of endogenous Zscan4 positivity and suggested that it is effective in maintaining the genome stability and potency of stem cells.

Research Products

• [Journal Article] Preoperative assessment of factors associated with difficulty in performing total laparoscopic hysterectomy. (2017)
  • Author(s): Saito A, Hirata T, Koga K, Takamura M, Fukuda S, Neriishi K, Pastorfide G, Harada M, Hirota Y, Wada-Hiraike O, Fujii T, Osuga Y
  • Journal Title: J Obstet Gynaecol Res. Volume: 43(2) Issue: 2 Pages: 320-329
  • DOI: 10.1111/jog.13198
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Drospirenone reduces inflammatory cytokines, vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) expression in human endometriotic stromal cells. (2017)
  • Author(s): Makabe T, Koga K, Miyashita M, Takeuchi A, Sue F, Taguchi A, Urata Y, Izumi G, Takamura M, Harada M, Hirata T, Hirota Y, Wada-Hiraike O, Fujii T, Osuga Y.
  • Journal Title: J Reprod Immunol Volume: 119 Pages: 44-48
  • DOI: 10.1016/j.jri.2016.12.002
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A Potential Role for Endoplasmic Reticulum Stress in Progesterone Deficiency in Obese Women. (2017)
  • Author(s): Takahashi N, Harada M, Hirota Y, Zhao L, Azhary JM, Yoshino O, Izumi G, Hirata T, Koga K, Wada-Hiraike O, Fujii T, Osuga Y.
  • Journal Title: Endocrinology Volume: 158 Pages: 84-97
  • DOI: 10.1210/en.2016-1511
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dienogest reduces proliferation, NGF expression and nerve fiber density in human adenomyosis. (2016)
  • Author(s): Takeuchi A, Koga K, Miyashita M, Makabe T, Sue F, Harada M, Hirata T, Hirota Y, Fujii T, Osuga Y.
  • Journal Title: Eur J Obstet Gynecol Reprod Biol Volume: 207 Pages: 157-161
  • DOI: 10.1016/j.ejogrb.2016.10.053
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Assisted reproductive technology pregnancy complications are significantly associated with endometriosis severity before conception: a retrospective cohort study. (2016)
  • Author(s): Fujii T, Wada-Hiraike O, Nagamatsu T, Harada M, Hirata T, Koga K, Fujii T, Osuga Y.
  • Journal Title: Reprod Biol Endocrinol. Volume: 3;14(1) Pages: 73-73
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mannose receptor is highly expressed by peritoneal dendritic cells in endometriosis. (2016)
  • Author(s): Izumi G, Koga K, Takamura M, Makabe T, Nagai M, Urata Y, Harada M, Hirata T, Hirota Y, Fujii T, Osuga Y.
  • Journal Title: Fertil Steril Volume: 107 Issue: 1 Pages: 167-173
  • DOI: 10.1016/j.fertnstert.2016.09.036
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Development of ovarian cancer after excision of endometrioma. (2016)
  • Author(s): Haraguchi H, Koga K, Takamura M, Makabe T, Sue F, Miyashita M, Urata Y, Izumi G, Harada M, Hirata T, Hirota Y, Wada-Hiraike O, Oda K, Kawana K, Fujii T, Osuga Y.
  • Journal Title: Fertil Steril Volume: 106 Issue: 6 Pages: 1432-1437
  • DOI: 10.1016/j.fertnstert.2016.07.1077
  • Peer Reviewed
• [Journal Article] Neutrophil depletion reduces endometriotic lesion formation in mice. (2016)
  • Author(s): Takamura M, Koga K, Izumi G, Urata Y, Nagai M, Hasegawa A, Harada M, Hirata T, Hirota Y, Wada-Hiraike O, Fujii T, Osuga Y.
  • Journal Title: Am J Reprod Immunol Volume: 76 Issue: 3 Pages: 193-198
  • DOI: 10.1111/aji.12540
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effects of 1,25-dihydroxy vitamin D3 on endometriosis. (2016)
  • Author(s): Miyashita M, Koga K, Izumi G, Sue F, Makabe T, Taguchi A, Nagai M, Urata Y, Takamura M, Harada M, Hirata T, Hirota Y, Wada-Hiraike O, Fujii T, Osuga Y.
  • Journal Title: J Clin Endocrinol Metab Volume: 101 Issue: 6 Pages: 2371-2379
  • DOI: 10.1210/jc.2016-1515
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A potential role of endoplasmic reticulum stress in development of ovarian hyperstimulation syndrome. (2016)
  • Author(s): Takahashi N, Harada M, Hirota Y, Zhao L, Yoshino O, Urata Y, Izumi G, Takamura M, Hirata T, Koga K, Wada-Hiraike O, Fujii T, Osuga Y.
  • Journal Title: Mol Cell Endocrinol Volume: 428 Pages: 161-169
  • DOI: 10.1016/j.mce.2016.03.032
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Resveratrol Enhances Apoptosis in Endometriotic Stromal Cells. (2016)
  • Author(s): Taguchi, A., Koga, K., Kawana, K., Makabe, T., Sue, F., Miyashita, M., Yoshida, M., Urata, Y., Izumi, G., Takamura, M., Harada, M., Hirata, T., Hirota, Y., Wada-Hiraike, O., Fujii, T., Osuga, Y
  • Journal Title: American Journal of Reproductive Immunology Volume: 75 Issue: 4 Pages: 486-492
  • DOI: 10.1111/aji.12489
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Vaginal Stenosis After Gonadotropin-Releasing Hormone Agonist Therapy During Treatment for Acute Lymphoblastic Leukemia. (2016)
  • Author(s): Sato M, Harada M, Oishi H, Wada-Hiraike O, Hirata T, Nagasaka K, Koga K, Fujii T, Osuga Y.
  • Journal Title: J Low Genit Tract Dis. Volume: 20(2) Issue: 2 Pages: 11-13
  • DOI: 10.1097/lgt.0000000000000175
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Four Cases of Postoperative Pneumothorax Among 2814 Consecutive Laparoscopic Gynecologic Surgeries: A Possible Correlation Between Postoperative Pneumothorax and Endometriosis. (2015)
  • Author(s): Hirata T, Nakazawa A, Fukuda S, Hirota Y, Izumi G, Takamura M, Harada M, Koga K, Wada-Hiraike O, Fujii T, Osuga Y.
  • Journal Title: J Minim Invasive Gynecol Volume: 22 Issue: 6 Pages: 980-984
  • DOI: 10.1016/j.jmig.2015.04.023
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Elective single-embryo transfer improves cumulative pregnancy outcome in young patients but not in women of advanced reproductive age. (2015)
  • Author(s): Fujimoto A, Morishima K, Harada M, Hirata T, Osuga Y, Fujii T.
  • Journal Title: J Assist Reprod Genet. Volume: 32(12) Issue: 12 Pages: 1773-1779
  • DOI: 10.1007/s10815-015-0598-8
  • Peer Reviewed
• [Journal Article] Simultaneous Detection and Evaluation of Four Subsets of CD4+ T Lymphocyte in Lesions and Peripheral Blood in Endometriosis. (2015)
  • Author(s): Takamura, M., Koga, K., Izumi, G., Hirata, T., Harada, M., Hirota, Y., Hiraike, O., Fujii, T., Osuga, Y
  • Journal Title: American Journal of Reproductive Immunology Volume: 74 Issue: 6 Pages: 480-486
  • DOI: 10.1111/aji.12426
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evidence of the activation of unfolded protein response in granulosa and cumulus cells during follicular growth and maturation. (2015)
  • Author(s): Harada, M., Nose, E., Takahashi, N., Hirota, Y., Hirata, T., Yoshino, O., Koga, K., Fujii, T., Osuga, Y
  • Journal Title: Gynecological Endocrinology Volume: 31 Issue: 10 Pages: 783-787
  • DOI: 10.3109/09513590.2015.1062862
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Drospirenone induces decidualization in human eutopic endometrial stromal cells and reduces DNA synthesis of human endometriotic stromal cells. (2015)
  • Author(s): Miyashita, M., Koga, K., Izumi, G., Makabe, T., Hasegawa, A., Hirota, Y., Hirata, T., Harada, M., Fujii, T., Osuga, Y
  • Journal Title: Fertility and Sterility Volume: 104 Issue: 1 Pages: 217-24
  • DOI: 10.1016/j.fertnstert.2015.03.023
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Concomitant ovarian drilling and oocyte retrieval by laparoendoscopic single-site surgery led to live birth using in vitro maturation of oocyte and transfer of frozen-thawed blastocyst in woman with polycystic ovary syndrome. (2014)
  • Author(s): Hirata T, Fujimoto A, Koga K, Wada-Hiraike O, Fujii T, Osuga Y.
  • Journal Title: J Obstet Gynaecol Res Volume: 40 Issue: 5 Pages: 1431-1435
  • DOI: 10.1111/jog.12365
  • Peer Reviewed
• [Journal Article] Efficacy of dienogest in the treatment of symptomatic adenomyosis: a pilot study. (2014)
  • Author(s): Hirata T, Izumi G, Takamura M, Fujii T, Osuga Y.
  • Journal Title: Gynecol Endocrinol Volume: 30 Issue: 10 Pages: 726729-726729
  • DOI: 10.3109/09513590.2014.926882
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] IL-1β increases expression of tryptophan 2,3-dioxygenase and stimulates tryptophan catabolism in endometrioma stromal cells. (2014)
  • Author(s): Urata Y, Koga K, Hirota Y, Akiyama I, Izumi G, Takamura M, Nagai M, Harada M, Hirata T, Yoshino O, Kawana K, Fujii T, Osuga Y.
  • Journal Title: Am J Reprod Immunol. Volume: 72 Issue: 5 Pages: 496-503
  • DOI: 10.1111/aji.12282
  • Peer Reviewed / Open Access
• [Journal Article] Dienogest reduces proliferation, aromatase expression and angiogenesis, and increases apoptosis in human endometriosis. (2014)
  • Author(s): Miyashita M, Koga K, Takamura M, Izumi G, Nagai M, Harada M, Hirata T, Hirota Y, Fujii T, Osuga Y.
  • Journal Title: Gynecol Endocrinol. Volume: 30 Issue: 9 Pages: 644-648
  • DOI: 10.3109/09513590.2014.911279
  • Peer Reviewed / Open Access
• [Journal Article] The Role of Bone Morphogenetic Protein 6 in Accumulation and Regulation of Neutrophils in the Human Ovary. (2014)
  • Author(s): Akiyama I, Yoshino O, Osuga Y, Shi J, Takamura M, Harada M, Koga K, Hirota Y, Hirata T, Fujii T, Saito S, Kozuma S.
  • Journal Title: Reproductive Sciences Volume: 21 Issue: 6 Pages: 772-777
  • DOI: 10.1177/1933719113518988
  • Peer Reviewed
• [Journal Article] Bone morphogenetic protein 7 increased vascular endothelial growth factor (VEGF)-a expression in human granulosa cells and VEGF receptor expression in endothelial cells. (2014)
  • Author(s): Akiyama I, Yoshino O et al.
  • Journal Title: Reprod Sci. Volume: 21(4) Issue: 4 Pages: 477-82
  • DOI: 10.1177/1933719113503411
  • Peer Reviewed
• [Journal Article] The outcome of infertility treatment in patients undergoing assisted reproductive technology after conservative therapy for endometrial cancer. (2014)
  • Author(s): Fujimoto A, Ichinose M, Harada M, Hirata T, Osuga Y, Fujii T.
  • Journal Title: J Assist Reprod Genet Volume: 31 Issue: 9 Pages: 1189-94
  • DOI: 10.1007/s10815-014-0297-x
  • Peer Reviewed
• [Presentation] Research platform focusing on endometriotic epithelial cells, (2017)
  • Author(s): Tetsuya Hirata
  • Organizer: 3rd Congress of SEUD
  • Place of Presentation: シンガポール
  • Year and Date: 2017-04-06
  • Int'l Joint Research / Invited
• [Presentation] 子宮内膜症上皮細胞にフォーカスした内膜症研究基盤の構築 (2017)
  • Author(s): 中澤 明里1）、平田 哲也1）、小田真由美2）、福田 晋也1）、錬石 和明1）、小阪 実生1）、洪 繁2）、洪 実2）、大須賀 穣1）、藤井 知行1）
  • Organizer: 第38回エンドメトリオーシス学会
  • Place of Presentation: 東京
  • Year and Date: 2017-01-21
• [Presentation] 子宮内膜症上皮細胞におけるペリオスチンの発現と機能の解析 (2017)
  • Author(s): 錬石 和明、平田 哲也、福田 晋也、中澤 明里、原田美由紀、廣田 泰、甲賀かをり、平池 修、大須賀 穣、藤井 知行
  • Organizer: 第38回エンドメトリオーシス学会
  • Place of Presentation: 東京
  • Year and Date: 2017-01-21
• [Presentation] 子宮内膜症マウスモデルにおける原始卵胞異常活性化に関する検討 (2017)
  • Author(s): 竹内亜利砂、甲賀かをり、佐竹絵里奈、真壁 友子、田口 歩、泉 玄太郎、原田美由紀、平田 哲也、廣田 泰、平池 修、大須賀 穣、藤井 知行
  • Organizer: 第38回エンドメトリオーシス学会
  • Place of Presentation: 東京
  • Year and Date: 2017-01-21
• [Presentation] 当院における thoracic endometriosis 23 例の検討 (2017)
  • Author(s): 福田 晋也、平田 哲也、高村 将司、久保田佳穂里、錬石 和明、中澤 明里、原田美由紀、廣田 泰、甲賀かをり、平池 修、大須賀 穣、藤井 知行
  • Organizer: 第38回エンドメトリオーシス学会
  • Place of Presentation: 東京
  • Year and Date: 2017-01-21