generation of iPS cells by preimplnatation specific genes

• Project/Area Number: 24791691
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• 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): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: stem cell / preimplantaion gene / iPS細胞 / ES細胞 / Zscan4 / iPS

Research Abstract

The generation of induced pluripotent stem cells (iPSCs) by the forced expression of defined transcription factors in somatic cells holds great promise for the future of regenerative medicine. However, the initial reprogramming mechanism is still poorly understood. Here we show that Zscan4, expressed transiently in 2-cell embryos and embryonic stem cells (ESCs), efficiently produces iPSCs from mouse embryo fibroblasts when coexpressed with Klf4, Oct4, and Sox2. Interestingly, the forced expression of Zscan4 is required only for the first few days of iPSC formation. Microarray analysis revealed transient and early induction of preimplantation-specific genes in a Zscan4-dependent manner. Our work indicates that Zscan4 is a previously unidentified potent natural factor that facilitates the reprogramming process and reactivates early embryonic genes.

Research Products

• [Journal Article] Follistatin is induced by IL-1βand TNF-αin stromal cells from endometrioma (2013)
  • Author(s): Akiyama I, Yoshino O, Osuga Y, Izumi G, Urata Y, Hirota Y, Hirata T, Harada M, Koga K, Ogawa K, Kozuma S
  • Journal Title: Reprod Sci Volume: 20(6) Issue: 6 Pages: 675-9
  • DOI: 10.1177/1933719112463253
  • Peer Reviewed
• [Journal Article] Cyclic stretch augments production of neutrophil chemokines and matrix metalloproteinase-1 in human uterine smooth muscle cells. (2013)
  • Author(s): Zhao Y1, Koga K, Osuga Y, Izumi G, Takamura M, Harada M, Hirata T, Hirota Y, Yoshino O, Fujii T, Kozuma S.
  • Journal Title: Am J Reprod Immunol. Volume: 69 Issue: 3 Pages: 240-7
  • DOI: 10.1111/aji.12061
  • Peer Reviewed
• [Journal Article] Cyclic Stretch Augments Production of Neutrophil Chemokines and Matrix Metalloproteinases-1 (MMP-1) from Human Decidual Cells, and the Production was Reduced by Progesterone. (2013)
  • Author(s): Zhao Y, Koga K, Osuga Y, Izumi G, Takamura M, Harada M, Hirata T, Hirota Y, Yoshino O, Inoue S, Fujii T, Kozuma S
  • Journal Title: Am J Reprod Immunol Volume: 69 Issue: 5 Pages: 454-462
  • DOI: 10.1111/aji.12092
  • Peer Reviewed
• [Journal Article] Interleukin-4 and prostaglandin E2 synergistically up-regulate 3β-hydroxysteroid dehydrogenase type 2 in endometrioma stromal cells (2013)
  • Author(s): Urata Y, Osuga Y, Akiyama I, Nagai M, Izumi G, Takamura M, Hasegawa A, Harada M, Hirata T, Hirota Y, Yoshino O, Koga K, Kozuma S
  • Journal Title: J Clin Endocrinol Metab Volume: 98(4) Issue: 4 Pages: 1583-90
  • DOI: 10.1210/jc.2012-3475
  • Peer Reviewed
• [Journal Article] Systematic repression of transcription factors reveals limited patterns of gene expression changes in ES cells (2013)
  • Author(s): Akira Nishiyama et al.
  • Journal Title: Scientific Reports Volume: 3 Issue: 1 Pages: 1390-1390
  • DOI: 10.1038/srep01390
  • Peer Reviewed
• [Journal Article] Zscan4 restores the developmental potency of embryonic stem cells (2013)
  • Author(s): Amano T, Hirata T, Falco G, Monti M, Sharova LV, Amano M, Sheer S, Hoang HG, Piao Y, Stagg CA, Yamamizu K, Akiyama T, Ko MS.
  • Journal Title: Nature communications Volume: 4 Issue: 1 Pages: 1966-1966
  • DOI: 10.1038/ncomms2966
  • Peer Reviewed
• [Journal Article] Zscan4 transiently reactivates early embryonic genes during the generation of induced pluripotent stem cells (2012)
  • Author(s): Hirata T , Amano T, Nakatake Y, Amano M, Piao Y, Hoang HG, Ko MS
  • Journal Title: Sci Rep Volume: 2 Issue: 1 Pages: 208-208
  • DOI: 10.1038/srep00208
  • NAID: 10030590982
  • Peer Reviewed
• [Journal Article] Proteinase-activated receptors in the endometrium and endometriosis (2012)
  • Author(s): Osuga Y, Hirota Y, Yoshino O, Hirata T , Koga K, Taketani Y
  • Journal Title: Front Biosci (Schol Ed) Volume: 4 Pages: 1201-12
• [Journal Article] Urata Y, Osuga Y, Izumi G, Takamura M, Koga K, Nagai M, Harada M, Hirata T, Hirota Y, Yoshino O, Taketani Y (2012)
  • Author(s): Interleukin-1β stimulates the secretion of thymic stromal lymphopoietin (TSLP) from endometrioma stromal cells: possible involvement of TSLP in endometriosis.
  • Journal Title: Hum Reprod Volume: 27 Issue: 10 Pages: 3028-35
  • DOI: 10.1093/humrep/des291
  • Peer Reviewed
• [Journal Article] The Localization and Regulation of Proprotein Convertase Subtilisin/Kexin (PCSK) 6 in Human Ovary. (2012)
  • Author(s): Akiyama I, Yoshino O, Osuga Y, Shi J, Hirota Y, Hirata T, Harada M, Koga K, Fujimoto A, Yano T, Taketani Y.
  • Journal Title: Am J Reprod Immunol. Volume: 68 Issue: 6 Pages: 491-498
  • DOI: 10.1111/aji.12003
  • Peer Reviewed
• [Presentation] Zscan4はiPS作製早期に着床前期胚特異的遺伝子を活性化する (2012)
  • Author(s): 平田哲也、天野朋和、天野美砂、中武悠樹、大須賀穣、武谷雄二、洪実
  • Organizer: 日本哺乳類卵子学会
  • Place of Presentation: 大阪
• [Presentation] Zscan4はiPS作製早期に着床前期胚特異的遺伝子を活性化する (2012)
  • Author(s): 平田哲也、天野朋和、天野美砂、中武悠樹、大須賀穣、武谷雄二、洪実
  • Organizer: 日本再生医療学会
  • Place of Presentation: 横浜