The mechanism of the acquisition of germ cell-specific epigenome and its reconstruction in vitro.

2012 Fiscal Year Final Research Report

• Project Area: The germline: its developmental cycle and epigenome network
• Project/Area Number: 20062011
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University (2009-2012); The Institute of Physical and Chemical Research (2008)
• Principal Investigator: SAITOU Mitinori 京都大学, 医学研究科, 教授 (80373306)
• Co-Investigator(Kenkyū-buntansha): OHINATA Yasuhide (70415107) ; UEDA Jun (80450394)
• Project Period (FY): 2008 – 2012
• Keywords: 発生・分化 / 遺伝子 / ゲノム / シグナル伝達 / 再生医学

Research Abstract

We clarified the mechanism underlying the specification of primordial germ cells (PGCs), the precursors both for spermatozoa and oocytes, in mice. Based on the knowledge obtained, we succeeded in reconstituting mouse germ cell specification pathway in culture by pluripotent stem cells including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). The induced PGC-like cells contributed to spermatozoa and oocytes, and to fertile offspring. We also clarified the role of PRDM14 in the maintenance of pluripotency in mouse ESCs.

Research Products

• [Journal Article] PRDM14 ensures naive pluripotency through dual regulation of signaling and epigenetic pathways in mouse embryonic stem cells (2013)
  • Author(s): Yamaji, M., Ueda, J., Hayashi, K., Ohta, H., Yabuta, Y., Kurimoto, K., Nakato, R., Shirahige, K., and Saitou, M
  • Journal Title: Cell Stem Cell Volume: 12 Pages: 368-382
  • DOI: DOI:10.1016/j.stem.2012.12.012
• [Journal Article] Replication-coupled passive DNA demethylation for the erasure of genome imprints in mice (2013)
  • Author(s): Kagiwada, S., Kurimoto, K., Hirota, T., Yamaji, M., and Saitou, M
  • Journal Title: The EMBO Journal Volume: 32 Pages: 340-353
  • DOI: DOI:10.1038/emboj.2012.331
• [Journal Article] Offspring from oocytes derived from in vitro primordial germ cell-like cells in mice (2012)
  • Author(s): Hayashi, K., Ogushi, S., Kurimoto, K., Shimamoto, S., Ohta, H., and Saitou, M
  • Journal Title: Science Volume: 338 Pages: 971-975
  • DOI: DOI:10.1126/science.1226889
• [Journal Article] Reconstitution of the mouse germ cell specification pathway in culture by pluripotent stem cells (2011)
  • Author(s): Hayashi, K., Ohta, H., Kurimoto, K., Aramaki, S., and Saitou, M
  • Journal Title: Cell Volume: 146 Pages: 519-532
  • DOI: DOI:DOI 10.1016/j.cell.2011.06.052
• [Journal Article] Drug-inducible gene recombination by the Dppa3-MER Cre MER transgene in the developmental cycle of the germ cell lineage in mice (2011)
  • Author(s): Hirota, T., Ohta, H., Shigeta, M., Niwa, H., and Saitou, M
  • Journal Title: Biology of Reproduction Volume: 85 Pages: 367-377
  • DOI: DOI:DOI 10.1095/biolreprod.110.090662
• [Journal Article] TDRD5 is required for retrotransposon silencing, chromatoid body assembly and spermiogenesis in mice (2011)
  • Author(s): Yabuta, Y., Ohta, H., Abe, T., Kurimoro, K., Chuma, S., and Saitou, M
  • Journal Title: The Journal of Cell Biology Volume: 192 Pages: 781-795
  • DOI: DOI:10.1083/jcb.201009043
• [Journal Article] Functional reconstruction of Nanos3 expression in the germ cell lineage by a novel transgenic reporter reveals distinct subcellular localizations of Nanos3 (2010)
  • Author(s): Yamaji, M., Tanaka, T., Shigeta, M., Chuma, S., Saga, Y., and Saitou, M
  • Journal Title: Reproduction Volume: 139 Pages: 381-393
  • DOI: DOI:10.1530/REP-09-0373
• [Journal Article] A signaling principle for the specification of the germ cell lineage in mice (2009)
  • Author(s): Ohinata, Y., Ohta, H., Shigeta, M., Yamanaka, K., Wakayama, T., and Saitou, M
  • Journal Title: Cell Volume: 137 Pages: 571-584
  • DOI: DOI:10.1016/j.cell.2009.03.014
• [Journal Article] Critical function of Prdm14 for the establishment of the germ cell lineage in mice (2008)
  • Author(s): Yamaji, M., Seki, Y., Kurimoto, K., Yabuta, Y., Yuasa, M., Shigeta, M., Yamanaka, K., Ohinata, Y., and Saitou, M
  • Journal Title: Nature Genetics Volume: 40 Pages: 1016-1022
  • DOI: DOI:10.1038/ng.186
• [Journal Article] Complex genome-wide transcription dynamics orchestrated by Blimp1 for the specification of the germ cell lineage in mice (2008)
  • Author(s): Kurimoto, K., Yabuta, Y., Ohinata, Y., Shigeta, M., Yamanaka, K., and Saitou, M
  • Journal Title: Genes & Development Volume: 22 Pages: 1617-1635
  • DOI: DOI:10.1101/gad.1649908
• [Presentation] Mechanism and reconstitution in vitro of germ cell specification in mice (2012)
  • Author(s): Saitou, M.
  • Organizer: EMBO/EMBL "From Functional Genomics to Systems Biology" meeting
  • Place of Presentation: Heidelberg, Germany
  • Year and Date: 2012-11-18
• [Presentation] Mechanism and reconstitution in vitro of germ cell specification in mice (2012)
  • Author(s): Saitou, M
  • Organizer: EMBO/EMBL Symposium
  • Place of Presentation: Heidelberg, Germany
  • Year and Date: 2012-10-16
• [Presentation] Mechanism and reconstitution in vitro of germ cell specification in mice (2012)
  • Author(s): Saitou, M
  • Organizer: The 4th EMBO meeting
  • Place of Presentation: Nice, France
  • Year and Date: 2012-09-25
• [Presentation] Towards in vitro reconstitution of mammalian germ cell development (2012)
  • Author(s): Saitou, M
  • Organizer: ISSCR 10^<th> Annual Meeting
  • Place of Presentation: 横浜
  • Year and Date: 2012-06-14
• [Presentation] Mechanism and reconstitution in vitro of germ cell specification in mice (2011)
  • Author(s): Saitou, M
  • Organizer: Stem Cells in Development and Disease Max-Delbruck-Center
  • Place of Presentation: Berlin-Buch, Germany
  • Year and Date: 2011-09-12
• [Presentation] Germ cell specification in mice in vivo and in vitro (2010)
  • Author(s): Saitou, M
  • Organizer: Cold Spring Harbor Laboratory Meeting on Germ Cells
  • Place of Presentation: Cold Spring Harbor Laboratory, New York, USA
  • Year and Date: 2010-10-05
• [Presentation] Germ cell specification in vivo and in vitro (2010)
  • Author(s): Saitou, M
  • Organizer: ISSCR 8^<th> Annual Meeting
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2010-06-18
• [Book] Primordial germ cells in mice (2012)
  • Author(s): Saitou, M., and Yamaji, M
  • Total Pages: 4
  • Publisher: CSH Perspectives in Biology
  • URL: DOI:10.1101/cshperspect.a008375
• [Book] A global single-cell cDNA amplification method for quantitative microarray analysis (2011)
  • Author(s): Kurimoto, K., and Saitou, M
  • Total Pages: 687, 91-111
  • Publisher: Methods in Molecular Biology
  • URL: DOI:10.1007/978-1-60761-944-4_7
• [Remarks]
  • URL: http://www.med.kyoto-u.ac.jp/organization-staff/research/doctoral_course/r-003/
• [Remarks]
  • URL: http://step.anat2.med.kyoto-u.ac.jp/
• [Patent(Industrial Property Rights)] METHOD OF INDUCING DIFFERENTIATION FROM PLURIPOTENT STEM CELLS TO GERM CELLS (2013)
  • Inventor(s): 斎藤通紀、中木文雄
  • Industrial Property Rights Holder: 国立大学法人京都大学
  • Industrial Property Number: 特許、61/771,619
  • Filing Date: 2013-03-01
  • Overseas
• [Patent(Industrial Property Rights)] METHOD OF INDUCING DIFFERENTIATION FROM PLURIPOTENT STEM CELLS TO GERM CELLS (2010)
  • Inventor(s): 斎藤通紀、林克彦
  • Industrial Property Rights Holder: 国立大学法人京都大学
  • Industrial Property Number: 特許、61/373,563
  • Filing Date: 2010-08-13
  • Overseas