Unveiling the mechanism of action of Blimp1, a transcriptional regulator that governs fates and homeostasis of diverse cell lineage

2013 Fiscal Year Final Research Report

• Project/Area Number: 21677003
• Research Category: Grant-in-Aid for Young Scientists (S)
• Allocation Type: Single-year Grants
• Research Field: Developmental biology
• Research Institution: Kyoto University
• Principal Investigator: SAITOU Mitinori 京都大学, 大学院・医学研究科, 教授 (80373306)
• Project Period (FY): 2009 – 2013
• Keywords: 発生・分化 / 遺伝子 / ゲノム / シグナル伝達 / 再生医学

Research Abstract

This study identified the mechanism of action of BLIMP1 and the epigenome dynamics for germ cell specification and development, with the establishment of a ChIP-seq method from a small number of cells, of in vitro primordial germ cell induction method, and of a drug-inducible gene-knockout strain during germ cell development. This study also explored the mechanism of action of BLIMP1 in various cell types including developing intestinal epithelial cells where BLIMP1 is expressed, and is uncovering BLIMP1 function in an integrated fashion.

Research Products

• [Journal Article] A mesodermal factor, T, specifies mouse germ cell fate by directly activating germline determinants (2013)
  • Author(s): Aramaki, S., Hayashi, K., Kurimoto, K., Ohta, H., Yabuta, Y., Iwanari, H., Mochizuki, Y., Hamakubo, T., Kato, Y., Shirahige, K., and Saitou, M
  • Journal Title: Developmental Cell Volume: 27 Pages: 516-529
  • DOI: DOI:10.1016/j.devcel.2013.11.001
• [Journal Article] Induction of the mouse germ cell fate by transcription factors in vitro (2013)
  • Author(s): Nakaki, F., Hayashi, K., Ohta, H., Kurimoto, K., Yabuta, Y., and Saitou, M
  • Journal Title: Nature Volume: 501 Pages: 222-226
  • DOI: DOI: 10.1038/nature12417
• [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: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: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
• [Presentation] Mechanism and reconstitution in vitro of germ cell development in mice (2014)
  • Author(s): Saitou, M
  • Organizer: Gordon Research Conference "Reprogramming Cell Fate"
  • Place of Presentation: Houston, USA
  • Year and Date: 2014-03-03
• [Presentation] Mechanism and reconstitution in vitro of germ cell development in mice (2013)
  • Author(s): Saitou, M
  • Organizer: SSR 2013 Annual Meeting
  • Place of Presentation: Montreal, Canada
  • Year and Date: 2013-07-25
• [Presentation] Mechanism and reconstitution in vitro of germ cell development in mice (2013)
  • Author(s): Saitou, M
  • Organizer: ISSCR 11^<th> Annual Meeting
  • Place of Presentation: Boston, USA
  • Year and Date: 2013-06-15
• [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 Cold Spring Harbor Laboratory
  • Place of Presentation: 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] Stepwise differentiation from naive state pluripotent stem cells to functional primordial germ cells through an epiblast-like state (2013)
  • Author(s): Hayashi, K., and Saitou, M
  • Total Pages: 1074, 175-183,
  • Publisher: Methods in Molecular Biology
• [Book] Primordial germ cells in mice (2012)
  • Author(s): Saitou, M., and Yamaji, M
  • Total Pages: 4
  • Publisher: CSH Perspectives in Biology
• [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
• [Remarks]
  • URL: http://www.med.kyoto-u.ac.jp/organization-staff/research/doctoral_course/r-003/
• [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