科学技術振興機構 さきがけ エピジェネティクスの制御と生命機能 エピジェネティクスの制御と生命機能さきがけ独立行政法人科学技術振興機構

研究成果

林 克彦(Katsuhiko Hayashi)

(corresponding author に*印をしています。)

原著欧文論文

  1. Hayashi K, Ohta H, Kurimoto K, Aramaki S, Saitou M. Reconstitution of the mouse germ cell specification pathway in culture by pluripotent stem cells. Cell. 2011 Aug 19;146(4):519-32.
  2. Villacorte M, Suzuki K, Hayashi K, de Sousa Lopes SC, Haraguchi R, Taketo MM, Nakagata N, Yamada G.Antagonistic crosstalk of Wnt/beta-catenin/Bmp signaling within the Apical Ectodermal Ridge (AER) regulates interdigit formation. Biochem Biophys Res Commun. 2010 Jan 22;391(4):1653-7.
  3. Hanina SA, Mifsud W, Down TA, Hayashi K, O'Carroll D, Lao K, Miska EA, Surani MA. Genome-wide identification of targets and function of individual MicroRNAs in mouse embryonic stem cells. PLoS Genet. 2010 Oct 21;6(10):e1001163.
  4. Bao S, Tang F, Li X, Hayashi K, Gillich A, Lao K, Surani MA. Epigenetic reversion of post-implantation epiblast to pluripotent embryonic stem cells Nature. 2009 Oct 29;461(7268):1292-5..
  5. Yeap LS, Hayashi K, Surani MA. ERG-associated protein with SET domain (ESET)-Oct4 interaction regulates pluripotency and represses the trophectoderm lineage. Epigenetics Chromatin. 2009 Oct 7;2(1):12
  6. Hayashi K and Surani MA Post-implantation epiblast-derived ES cells composed of primordial germ cell-lineage coupled with epigenetic reprogramming. Development 2009 Nov; 136(21):3549-3556
  7. Nakayama J, Yamamoto M, Hayashi K, Satoh H, Bundo K, Kubo M, Goitsuka R, Farrar MA, Kitamura D. BLNK suppresses pre-B-cell leukemogenesis through inhibition of JAK3. Blood. 2009 Feb 12;113(7):1483-92.
  8. Hayashi K, Chuva de Sousa Lopes SM, Tang F, Surani MA. Heterogeneous expression of Stella reveals a unique epigenetic and developmental state of pluripotent embryonic stem cells. Cell Stem Cell 2008 Oct 9;3(4):391-401.
  9. Watanabe M, Takagi Y, Kotani M, Hara Y, Inamine A, Hayashi K, Ogawa S, Takeda K, Tanabe K, Abe R. Down-regulation of ICOS ligand by interaction with ICOS functions as a regulatory mechanism for immune responses. J Immunol. 2008 Apr 15;180(8):5222-34.
  10. Hayashi K, Chuva de Sousa Lopes SM, Kaneda M, Tang F, Hajkova P, Lao K, O'Carroll D, Das PP, Tarakhovsky A, Miska EA, Surani MA. MicroRNA Biogenesis Is Required for Mouse Primordial Germ Cell Development and Spermatogenesis. PLoS ONE. 2008 Mar 5;3(3):e1738.
  11. Chuva de Sousa Lopes SM, Hayashi K, Shovlin TC, Mifsud W, Surani MA, McLaren A. X Chromosome Activity in Mouse XX Primordial Germ Cells. PLoS Genet. 2008 Feb 8;4(2):e30
  12. Hidano S, Sasanuma H, Ohshima K, Seino K, Kumar L, Hayashi K, Hikida M, Kurosaki T, Taniguchi M, Geha RS, Kitamura D, Goitsuka R. Distinct regulatory functions of SLP-76 and MIST in NK cell cytotoxicity and IFN-gamma production. Int Immunol. 2008 Mar;20(3):345-52.
  13. de Sousa Lopes SM, Hayashi K, Surani MA. Proximal visceral endoderm and extraembryonic ectoderm regulate the formation of primordial germ cell precursors. BMC Dev Biol. 2007 Dec 20;7:140
  14. Yamamoto M, Hayashi K, Nojima T, Matsuzaki Y, Kawano Y, Karasuyama H, Goitsuka R, Kitamura D. BASH-novel PKC-Raf-1 pathway of pre-BCR signaling induces {kappa} gene rearrangement. Blood. 2006 108(8):2703-2711
  15. Tanaka S, Tsukada J, Suzuki W, Hayashi K, Tanigaki K, Tsuji M, Inoue H, Honjo T, Kubo M. The interleukin-4 enhancer CNS-2 is regulated by Notch signals and controls initial expression in NKT cells and memory-type CD4 T cells. Immunity. 2006 24:689-701.
  16. Nojima T, Hayashi K, Goitsuka R, Nakayama K, Nakayama K, Kitamura D.
  17. Sasanuma H, Tatsuno A, Hidano S, Ohshima K, Matsuzaki Y, Hayashi K, Lowell CA, Kitamura D, Goitsuka R. Dual function for the adaptor MIST in IFN-{gamma} production by NK and CD4+NKT cells regulated by the Src-kinase Fgr. Blood. 2006 107(9): 3647-5
  18. Hayashi K, Yoshida K, Matsui Y. A Histone H3 methyltransferase controls epigenetic events required for meiotic prophase. Nature. 2005 438: 374-378.
  19. Fujimaki R, Hayashi K, Watanabe N, Yamada T, Toyama Y, Tezuka, K and Hozumi N. Expression of Cre recombinase in the mouse developing chondrocytes driven by the mouse α2(XI) collagen promoter. J. Bone Miner. Metab 2005 .23: 270-273.
  20. Seki Y, Hayashi K, Ito K, Mizugaki M, Saitou M, Matsui Y, Extensive and orderly reprogramming of genome-wide chromatin modifications associated with specification and early development of germ cells in mice. Dev. Biol. 2005 278 440-458
  21. Hayashi K, Nojima T, Goitsuka R and Kitamura D. Impaired Receptor Editing in the Primary B Cell Repertoire of BASH-Deficient Mice. J Immunol. 2004 173(10):5980-5988.
  22. Okamura D, Hayashi K, Matsui Y. Mouse Epiblast Change responsiveness to BMP4 signal required for PGC formation through functions of extraembryonic ectoderm. Mol Reprod Dev. 2005 Jan;70(1):20-29
  23. Seki N, Miyazaki M, Suzuki W, Hayashi K, Arima K, Myburgh E, Izuhara K, Brombacher F, Kubo M. IL-4-induced GATA-3 expression is a time-restricted instruction switch for Th2 cell differentiation. J Immunol. 2004 172(10):6158-6166.
  24. Yamamoto M, Nojima T, Hayashi K, Goitsuka R, Furukawa K, Azuma T, Kitamura D. BASH-deficient mice: limited primary repertoire and antibody formation, but sufficient affinity maturation and memory B cell generation. in anti-NP response. Int Immunol. 2004 Aug;16(8):1161-71
  25. Hayashi K., Yamamoto M., Nojima T., Goitsuka R., Kitamura D. Distinct signaling requirements for Dmu selection, IgH allelic exclusion, pre-B cell transition, and tumor suppression in B cell progenitors. Immunity. 2003 Jun;18(6):825-36.
  26. Johmura S, Oh-hora M, Inabe K, Nishikawa Y, Hayashi K, Vigorito E, Kitamura D, Turner M, Shingu K, Hikida M, Kurosaki T. Regulation of Vav localization in membrane rafts by adaptor molecules Grb2 and BLNK. Immunity. 2003 Jun;18(6):777-787.
  27. Seki Y, Inoue H, Nagata N, Hayashi K, Fukuyama S, Matsumoto K, Komine O, Hamano S, Himeno K, Inagaki-Ohara K, Cacalano N, O'Garra A, Oshida T, Saito H, Johnston JA, Yoshimura A, Kubo M. SOCS-3 regulates onset and maintenance of T(H)2-mediated allergic responses. Nature Med. 2003 Aug;9(8):1047-1054.
  28. Matsumoto A, Seki Y, Watanabe R, Hayashi K, Johnston JA, Harada Y, Abe R, Yoshimura A, Kubo M. A role of suppressor of cytokine signaling 3 (SOCS3/CIS3/SSI3) in CD28-mediated interleukin 2 production. J Exp Med. 2003 Feb 17;197(4):425-436.
  29. Hayashi K*, Kobayashi T, Umino T, Goitsuka R, Matsui Y, Kitamura D. SMAD1 signaling is critical for initial commitment of germ cell lineage from mouse epiblast. Mech Dev. 2002 Oct;118(1-2):99-109.
  30. Seki Y, Hayashi K, Matsumoto A, Seki N, Tsukada J, Ransom J, Naka T, Kishimoto T, Yoshimura A, Kubo M. Expression of the suppressor of cytokine signaling-5 (SOCS5) negatively regulates IL-4-dependent STAT6 activation and Th2 differentiation. Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13003-13008
  31. Hayashi K, Nittono R, Kobayashi T, Kitamura D. A conventional method to rescue from embryonic lethality for analysis of gene function in vivo. J Reprod.Engneering. 2001 Vol.4 (1) 168-174
  32. Harada Y, Tokushima M, Matsumoto Y, Ogawa S, Otsuka M, Hayashi K, Weiss BD, June CH, Abe R. Critical requirement for the membrane-proximal cytosolic tyrosine residue for CD28-mediated costimulation in vivo. J Immunol 2001 Mar 15;166(6):3797-3803
  33. Terauchi A, Hayashi K, Kitamura D, Kozono Y, Motoyama N, Azuma T. A Pivotal Role for DNase I-Sensitive Regions 3b and/or 4 in the Induction of Somatic Hypermutation of IgH Genes. J Immunol 2001 Jul 15;167(2):811-820
  34. Hayashi K, Nittono R, Okamoto N, Tsuji S, Hara Y, Goitsuka R, Kitamura D The B cell-restricted adaptor BASH is required for normal development and antigen receptor-mediated activation of B cells. Proc Natl Acad Sci U S A 2000 Mar 14;97(6):2755-60
  35. Goitsuka R, Kanazashi H, Sasanuma H, Fujimura Yi, Hidaka Y, Tatsuno A, Ra C, Hayashi K, Kitamura D. A BASH/SLP-76-related adaptor protein MIST/Clnk involved in IgE receptor-mediated mast cell degranulation. Int Immunol 2000 Apr;12(4):573-580
  36. Hayashi K.,Maehara M.,Kitamura D.,Ogawa S. The fate of foreign gene injected into testis.; analysis of expression and existence in spermatozoa, embryos and mice by Cre-loxP system. J Reprod.Engneering. 2000 Vol.3 (1) 111-123
  37. Hayashi K.,Maehara M.,Kitamura D.,Ogawa S. The expression of exogenous DNA introduced into testis in embryos and newborns. Jpn.J.Fertil.Steril.2000 (in Japanese)
  38. Chang K.,Ikeda A.,Hayashi K.,Furuhata Y.,Nishihara M.,Ohta A.,Ogawa S.,Takahashi M. Production of transgenic rats and mice by the testis mediated gene transfer. J.Reprod.Dev 1999 45:29-4536
  39. Chang K.,Ikeda A.,Hayashi K.,Furuhata Y.,Bannai M.,Nishihara M.,Ohta A.,Ogawa S.,Takahashi M. Possible mechanisms for the testis mediated gene transfer as a new method for producing transgenic animals. J.Reprod.Dev 1999 4537-4542
  40. Hayashi K., Maehara, M., Tada, N., Ogawa, S. and Kitamura, D.: Analysis of foreign DNA transferred by direct injection into mouse testis. J. Reprod. Engneering, 2: 21-24, 1998.
  41. Ogawa S., Tada N., Hayashi K., Iwaya M. ,Sato M.,Saito H.,Ohta A.,Takahashi M.and Kurihara T. ;Posibility of testis mediated gene transfer as an alternative method for highly efficient production of transgenic animals. J Reprod.Engneering. 1998 vol1 pp1-11
  42. Hayashi K. Katoh T. Sakane J. Shyoso O. Iwaya M. Ushijima H. Tada N.Sato M. Acquisition of cloned bovines of defined sex by repeated cycles of nuclear transfer. Jpn.J.Fertil.Steril.1996 41:178-185
  43. Hayashi K.,Yamada H.,Kurihara T.,Tada N.,Ogawa S. Expression of exogeneous DNA in mouse embryos surviving after in vitro selection with G-418. J.Reprod.Dev 1995 41:293-298
  44. Ogawa,S.,Hayashi K.,Tada,N.,Sato,M. Gene expression in blastocysts following direct injection of DNA into testis. J.Reprod.Dev 1995 41:379-382
  45. Tada,N.,Sato,M.,Hayashi K.,Kasai,K.,Ogawa,S. In vitro selection of transgenic mouse embryos in the presence of G-418. Transgenics 1995 1:585-540
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総説/欧文

  1. Gillich A, Hayashi K*. Switching stem cell state through programmed germ cell reprogramming. Differentiation. 2011 Feb 15. Review
  2. Hayashi K and Surani MA. Resetting the epigenome beyond pluripotency in the germ line. Cell Stem Cell 2009 Jun 5;4(6):493-498 Review
  3. Surani MA, Durcova-Hills G, Hajkova P, Hayashi K, Tee WW. Germ Line, Stem Cells, and Epigenetic Reprogramming. Cold Spring Harb Symp Quant Biol. 2008 Nov 6.
  4. Hayashi K, de Sousa Lopes SM, Surani MA. Germ cell specification in mice. Science. 2007 316:394-396. Review
  5. Surani MA, Hayashi K, Hajkova P. Genetic and epigenetic regulators of pluripotency. Cell 2007 128:747-762. Review
  6. Matsui Y, Hayashi K. Epigenetic regulation for the induction of meiosis. Cell Mol Life Sci. 2007 Feb;64(3):257-262. Review
  7. Hayashi K, Matsui Y. Meisetz, a novel histone tri-methyltransferase, regulates meiosis-specific epigenesis. Cell Cycle. 2006 5(6):615-620 Review
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総説/日本語

  1. 林克彦;体内および体外における始原生殖細胞の初期発生 日本哺乳動物卵子学会誌 Vol. 26 (2009) , No. 4 171-177
  2. 林克彦, 松居靖久;生殖細胞系列特異的なヒストン修飾酵素と減数分裂 蛋白質・核酸・酵素,51(5),(2006),441-445
  3. 松居靖久, 林克彦;【再生医学 臨床と研究の最前線】 基礎編 配偶子形成 生殖細胞分化におけるエピジェネティックな制御 医学のあゆみ,217(5),(2006),593-598
  4. 松居靖久, 林克彦;ヒストンメチル化酵素Meisetzによる減数分裂の制御 ブレイン・テクノニュース,115,(2006),25-29
  5. 林克彦;減数分裂の分子基盤と異常 大阪府立母子保健総合医療センター雑誌 2005年号
  6. 林克彦、松居靖久;減数分裂の進行に必須な新規ヒストンメチル化酵素Meisetz 細胞工学Vol.25 No.1 (2006)
  7. 林克彦、松居靖久;マウス生殖細胞系列のエピジェネティクスと減数分裂の異常 実験医学 ,23(5),(2005),712-718
  8. 林克彦、後飯塚僚;B細胞の活性化とBASH 臨床免疫、32(4):411-416(1999)
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招待講演

  1. 林克彦:ES/iPS細胞を用いた体外培養による始原生殖細胞分化の再構築
    第38回幹細胞治療研究フォーラム 2011年6月16日 東京、東京大学医科学研究所
  2. 林克彦:多能性幹細胞から生殖細胞への分化- 発生モデルの構築と応用への基盤整備 -
    2010年度生殖工学会学術集会 2010年11月27日 神奈川、麻布大学
  3. 林克彦:多能性幹細胞の自己増殖と生殖細胞への分化
    日本哺乳動物卵子学会 2010年5月29日 新潟、朱鷺メッセ
  4. 林克彦:胚性幹細胞の不均一性と分化能
    セミナー 2009年3月11日 神奈川、横浜市立大学
  5. 林克彦:胚性幹細胞のゆらぎと始原生殖細胞への不可逆的分化
    セミナー 2009年3月10日 宮城、東北大学加齢医学研究所