generation of iPS cells by preimplnatation specific genes

2013 Fiscal Year Final Research Report

• 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
• Keywords: stem cell / preimplantaion gene / iPS細胞 / ES細胞

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-1β and TNF-α in 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) Pages: 675-9
  • DOI: 10.1177/1933719112463253
• [Journal Article] Cyclic stretch augments production of neutrophil chemokines and matrix metalloproteinase-1 in human uterine smooth muscle cells (2013)
  • Author(s): Zhao Y, 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(3) Pages: 240-7
  • DOI: 10.1111/aji.12061
• [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(5) Pages: 454-62
  • DOI: 10.1111/aji.12092
• [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) Pages: 1583-90
  • DOI: 10.1210/jc.2012-3475
• [Journal Article] Systematic repression of transcription factors reveals limited patterns of gene expression changes in ES cells (2013)
  • Author(s): Nishiyama A, Sharov AA, Piao Y, Amano M, Amano T, Hoang HG, Binder BY, Tapnio R, Bassey U, Malinou JN, Correa-Cerro LS, Yu H, Xin L, Meyers E, Zalzman M, Nakatake Y, Stagg C, Sharova L, Qian Y, Dudekula D, Sheer S, Cadet JS, Hirata T , Yang HT, Goldberg I, Evans MK, Longo DL, Schlessinger D, Ko MS
  • Journal Title: Sci Rep Volume: 3 Pages: 1390
  • DOI: 10.1038/srep01390
• [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 Pages: 208
  • DOI: 10.1038/srep00208
• [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] Interleukin-1β stimulates the secretion of thymic stromal lymphopoietin (TSLP) from endometrioma stromal cells : possible involvement of TSLP in endometriosis (2012)
  • Author(s): Urata Y, Osuga Y, Izumi G, Takamura M, Koga K, Nagai M, Harada M, Hirata T , Hirota Y, Yoshino O, Taketani Y
  • Journal Title: Hum Reprod Volume: 27(10) Pages: 3028-35
  • DOI: 10.1093/humrep/des291
• [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(6) Pages: 491-8
  • DOI: 10.1111/aji.12003