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Elucidation of the mechanisms underlying maintenance of hematopoietic stem cell hibernation

Research Project

Project/Area Number 21249059
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionThe University of Tokyo

Principal Investigator

NAKAUCHI Hiromitsu  東京大学, 医科学研究所, 教授 (40175485)

Co-Investigator(Kenkyū-buntansha) OTSU Makoto  東京大学, 医科学研究所, 特任准教授 (30361330)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥41,210,000 (Direct Cost: ¥31,700,000、Indirect Cost: ¥9,510,000)
Fiscal Year 2011: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2010: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2009: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000)
Keywords造血幹細胞 / CD34陽性細胞 / 骨髄微小環境 / 非髄鞘シュワン細胞 / GFAP陽性細胞 / 白血病幹細胞 / 冬眠 / 骨髄ニッチ / FOXO転写因子 / 脂質ラフト / TGFβ / 冬眠機構 / smad signaling
Research Abstract

Hematopoietic stem cells(HSCs) reside in a bone marrow niche in a nondividing state, from which they occasionally arise to undergo cell division. Yet, the mechanism underlying this unique feature remains largely unknown. We screened candidate niche signals that inhibit lipid raft clustering, and identified that transforming growth factor-β(TGF-β) efficiently induces HSC hibernation ex vivo. From these data, we uncovered a critical role for TGF-βas a candidate niche signal in the control of HSC hibernation and provided TGF-βas a novel tool for ex vivo modeling of the HSC niche. TGF-βis produced as a latent form by a variety of cells, so we next searched for those that express activator molecules for latent TGF-β. Nonmyelinating Schwann cells in bone marrow(BM) proved responsible for the activation. These glial cells ensheathed autonomic nerves, expressed HSC niche factor genes, and were in contact with a substantial proportion of HSCs. Autonomic nerve denervation reduced the number of these active TGF-β-producing cells and led to rapid loss of HSCs from BM. Collectively, we for the first time demonstrated that glial cells are components of a BM niche and maintain HSC hibernation by regulating activation of latent TGF-β.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (87 results)

All 2012 2011 2010 2009

All Journal Article (61 results) (of which Peer Reviewed: 61 results) Presentation (22 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 4 results)

  • [Journal Article] A Differentiation Checkpoint Limits Hematopoietic Stem Cell Self-Renewal in Response to DNA Damage2012

    • Author(s)
      Wang J, Sun Q, Morita Y, Jiang H, Gros A, Lechel A, Hildner K, Guachalla LM, Gompf A, Hartmann D, Schambach A, Wuestefeld T, Dauch D, Schrezenmeier H, Hofmann WK, Nakauchi H, Ju Z, Kestler HA, Zender L, Rudolph KL.
    • Journal Title

      Cell

      Volume: 148 Pages: 1001-1014

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lethal myelofibrosis induced by Bmi1-deficient hematopoietic cells unveils a tumor suppressor function of the polycomb group genes2012

    • Author(s)
      Oguro H, Yuan J, Tanaka S, Miyagi S, Mochizuki-Kashio M, Ichikawa H, Yamazaki S, Koseki H, Nakauchi H, Iwama A.
    • Journal Title

      J Exp Med

      Volume: 209 Pages: 445-54

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Plasmin inhibitor reduces lymphoid tumor growth by suppressing matrixmetallproteinase-9 dependent CD11b+/F4/80+ myeloid cell recruitment2012

    • Author(s)
      Ishihara M, Heissig B, Nishida C, Rosenkvist J, Tashiro Y, Ohki M, Wanaka K, Tsuda Y, Okada Y, Nakauchi H, Hattori K
    • Journal Title

      Leukemia

      Volume: 26 Issue: 2 Pages: 332-339

    • DOI

      10.1038/leu.2011.203

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lethal myelofibrosis induced by Bmil-deficient hematopoietic cells unveils a tumor suppressor function of the polycomb group genes2012

    • Author(s)
      Oguro H, Yuan J, Tanaka S, Miyagi S, Mochizuki-Kashio M, Ichikawa H, Yamazaki S, Koseki H, Nakauchi H, Iwama A
    • Journal Title

      J Exp Med

      Volume: 209 Pages: 445-54

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nonmyelinating Schwann cells maintain hematopoietic stem cell hibernation in the bone marrow niche2011

    • Author(s)
      Yamazaki S, Ema H, Karlsson G, Yamaguchi T, Miyoshi H, Shioda S, Taketo MM, Karlsson S, Iwama A, Nakauchi H.
    • Journal Title

      Cell

      Volume: 147 Pages: 1146-58

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Homeostasis of hematopoietic stem cells regulated by the myeloproliferative disease associated-gene product Lnk/Sh2b3 via Bcl-xL2011

    • Author(s)
      Suzuki N, Yamazaki S, Ema H, Yamaguchi T, Nakauchi H, Takaki S.
    • Journal Title

      Exp Hematol

      Volume: 40 Pages: 166-74

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Integrin-αvβ3 regulates thrombopoietin-mediated maintenance of hematopoietic stem cells2011

    • Author(s)
      Umemoto T, Yamato M, Ishihara J, Shiratsuchi Y, Utsumi M, Morita Y, Tsukui H, Terasawa M, Shibata T, Nishida K, Kobayashi Y, Petrich BG, Nakauchi H, Eto K, Okano T.
    • Journal Title

      Blood

      Volume: 119 Pages: 83-94

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ex vivo expansion of human hematopoietic stem cells by garcinol, a potent inhibitor of histone acetyltransferase2011

    • Author(s)
      Nishino T, Wang C, Mochizuki-Kashio M, Osawa M, Nakauchi H, Iwama A.
    • Journal Title

      PLoS One

      Volume: 6

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Frequent pathway mutations of splicing machinery in myelodysplasia2011

    • Author(s)
      Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R, Sato Y, Sato-Otsubo A, Kon A, Nagasaki M, Chalkidis G, Suzuki Y, Shiosaka M, Kawahata R, Yamaguchi T, Otsu M, Obara N, Sakata-Yanagimoto M, Ishiyama K, Mori H, Nolte F, Hofmann WK, Miyawaki
    • Journal Title

      Nature

      Volume: 478 Pages: 64-69

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hair follicle stem cells provide a functional niche for melanocyte stem cells2011

    • Author(s)
      Tanimura S, Tadokoro Y, Inomata K, Binh NT, Nishie W, Yamazaki S, Nakauchi H, Tanaka Y, McMillan JR, Sawamura D, Yancey K, Shimizu H, Nishimura EK
    • Journal Title

      Cell Stem Cell

      Volume: 8 Pages: 177-87

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Functional characterization of hematopoietic stem cells in the spleen2011

    • Author(s)
      Morita Y, Iseki A, Okamura S, Suzuki S, Nakauchi H, Ema H
    • Journal Title

      Exp Hematol

      Volume: 39 Pages: 351-359

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Development of defective and persistent sendai virus vector : a unique gene delivery/expression system ideal for cell reprogramming2011

    • Author(s)
      Nishimura K, Sano M, Ohtaka M, Furuta B, Umemura Y, Nakajima Y, Ikehara Y, Kobayashi T, Segawa H, Takayasu S, Sato H, Motomura K, Uchida E, Kanayasu-Toyoda T, Asashima M, Nakauchi H, Yamaguchi T, Nakanishi M
    • Journal Title

      J Biol Chem

      Volume: 11 Pages: 4760-4760

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ex vivo expansion of human hematopoietic stem cells by garcinol, a potent inhibitor of histone acetyltransferase2011

    • Author(s)
      Nishino T, Wang C, Mochizuki-Kashio M, Osawa M, Nakauchi H, Iwama A
    • Journal Title

      PLoS One

      Volume: 6 Issue: 9 Pages: e24298-e24298

    • DOI

      10.1371/journal.pone.0024298

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of defective and persistent sendai virus vector : a unique genedelivery/expression system ideal for cell reprogramming.2011

    • Author(s)
      Nishimura K, Sano M, OhtakaM, Furuta B, Umemura Y, Nakajima Y, Ikehara Y, Kobayashi T, Segawa H, Takayasu S, Sato H, MotomuraK, Uchida E, Kanayasu-ToyodaT, Asashima M, Nakauchi H, Yamaguchi T, Nakanishi M.
    • Journal Title

      JBiol Chem

      Volume: 286 Pages: 4760-71

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional characterization of hematopoietic stem cells in the spleen.2011

    • Author(s)
      Morita Y, Iseki A, Okamura S, Suzuki S, Nakauchi H, Ema H.
    • Journal Title

      Exp Hematol

      Volume: 39 Pages: 351-359

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transient activation of c-MYC expression is critical for efficient platelet generation from human induced pluripotent stem cells2010

    • Author(s)
      Takayama N, Nishimura S, Nakamura S, Shimizu T, Ohnishi R, Endo H, Yamaguchi T, Otsu M, Nishimura K, Nakanishi M, Sawaguchi A, Nagai R, Takahashi K, Yamanaka S, Nakauchi H, Eto K
    • Journal Title

      J Exp Med

      Volume: 207 Pages: 2817-30

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reprogramming adult hematopoietic cells2010

    • Author(s)
      Kaneko S, Otsu M, Nakauchi H
    • Journal Title

      Opin Hematol

      Volume: 17 Pages: 271-5

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Deregulated intracellular signaling by mutated c-CBL in myeloid neoplasms2010

    • Author(s)
      Ogawa S, Shih LY, Suzuki T, Otsu M, Nakauchi H, Koeffler HP, Sanada M
    • Journal Title

      Clin Cancer Res

      Volume: 16 Pages: 3825-31

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Downregulation of ZEB1 and overexpression of Smad7 contribute to resistance to TGF-beta1-mediated growth suppression in adult T-cell leukemia/lymphoma2010

    • Author(s)
      Nakahata S, Yamazaki S, Nakauchi H, Morishita K.
    • Journal Title

      Oncogene

      Volume: 29 Pages: 4157-69

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment2010

    • Author(s)
      Morita Y, Ema H, Nakauchi H
    • Journal Title

      J Exp Med

      Volume: 207 Pages: 1173-82

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] FET family proto-oncogene Fus contributes to self-renewal of hematopoietic stem cells2010

    • Author(s)
      Sugawara T, Oguro H, Negishi M, Morita Y, Ichikawa H, Iseki T, Yokosuka O, Nakauchi H, Iwama A
    • Journal Title

      Exp Hematol

      Volume: 38 Pages: 696-706

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Koeffler HP, Gain-of-function c-CBL mutations associated with uniparental disomy of 11q in myeloid neoplasms2010

    • Author(s)
      Ogawa S, Sanada M, Shih LY, Suzuki T, Otsu M, Nakauchi H
    • Journal Title

      Cell Cycle

      Volume: 9 Pages: 1051-6

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Poised lineage specification in multipotential hematopoietic stem and progenitor cells by the polycomb protein Bmil2010

    • Author(s)
      Oguro H, Yuan J, Ichikawa H, Ikawa T, Yamazaki S, Kawamoto H, Nakauchi H, Iwama A
    • Journal Title

      Cell Stem Cell

      Volume: 6 Pages: 279-86

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tissue type plasminogen activator regulates myeloid-cell dependent neoangiogenesis during tissue regeneration2010

    • Author(s)
      Ohki M, Ohki Y, Ishihara M, Nishida C, Tashiro Y, Akiyama H, Komiyama H, Lund LR, Nitta A, Yamada K, Zhu Z, Ogawa H, Yagita H, Okumura K, Nakauchi H, Werb Z, Heissig B, Hattori K
    • Journal Title

      Blood

      Volume: 115 Pages: 4302-12

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lnk regulates integrin alphaIIbbeta3 outside-in signaling in mouse platelets, leading to stabilization of thrombus development in vivo2010

    • Author(s)
      Takizawa H, Nishimura S, Takayama N, Oda A, Nishikii H, Morita Y, Kakinuma S, Yamazaki S, Okamura S, Tamura N, Goto S, Sawaguchi A, Manabe I, Takatsu K, Nakauchi H, Takaki S, Eto K
    • Journal Title

      J Clin Invest

      Volume: 120 Pages: 179-90

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lnk regulates integrin alphallbbeta3 outside-in signaling in mouse platelets, leading to stabilization of thrombus development in vivo.2010

    • Author(s)
      Takizawa H, Nishimura S, Takayama N, Oda A, Nishikii H, Morita Y, Kakinuma S, Yamazaki S, Okamura S, Tamura N, Goto S, Sawaguchi A, Manabe I, Takatsu K, NakauchiH, Takaki S, Eto K.
    • Journal Title

      J Cln Invest

      Volume: 120 Pages: 179-190

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tissue type plasminogen activator regulates myeloid-cell dependent neoangiogenesis during tissue regeneration.2010

    • Author(s)
      Ohki M, Ohki Y, Ishihara M, Nishida C, Tashiro Y, AkiyamaH, Komiyama H, Lund LR, NittaA, Yamada K, Zhu Z, Ogawa H, Yagita H, Okumura K, NakauchiH, Werb Z, Heissig B, Hattori K.
    • Journal Title

      Blood

      Volume: 115 Pages: 4302-12

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Poised lineage specification in multipotential hematopoietic stem and progenitor cells by the polycomb protein Bmil.2010

    • Author(s)
      Oguro H, Yuan J, Ichikawa H, Ikawa T, Yamazaki S, Kawamoto H, Nakauchi H, Iwama A.
    • Journal Title

      Cell Stem Cell

      Volume: 6 Pages: 279-286

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gain-of-function c-CBL mutations associated with uniparental disomy of 11q in myeloid neoplasms.2010

    • Author(s)
      Ogawa S, Sanada M, Shih LY, Suzuki T, Otsu M, Nakauchi H, Koeffler HP.
    • Journal Title

      Cell Cycle

      Volume: 9

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] FET family proto-oncogene Fus contributes to self-renewal of hematopoietic stem cel.2010

    • Author(s)
      Sugawara T, Oguro H, NegishiM, Morita Y, Ichikawa H, IsekiT, Yokosuka 0, Nakauchi H, Iwama A.
    • Journal Title

      Exp Hematol

      Volume: 38 Pages: 696-706

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment.2010

    • Author(s)
      Morita Y, Ema H, Nakauchi H.
    • Journal Title

      J Exp Med

      Volume: 207 Pages: 1173-1182

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rat transgenesis via embryonic stem cells electroporated with the Kusabira-orange gene2010

    • Author(s)
      Hirabayashi M, Kato M, Sanbo M, Kobayashi T, Hochi S, Nakauchi H.
    • Journal Title

      Mol Reprod Dev

      Volume: 77 Pages: 474-474

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Downregulation of ZEB1 and overexpression of Smad7 contribute to resistance to TGF-betal-mediated growth suppression in adult T-cell leukemia/lymphoma.2010

    • Author(s)
      Nakahata S, Yamazaki S, Nakauchi H, Morishita K.
    • Journal Title

      Oncogene

      Volume: 29 Pages: 4157-69

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deregulated intracellular signaling by mutated c-CBL in myeloid neoplasms.2010

    • Author(s)
      Ogawa S, Shih LY, Suzuki T, Otsu M, Nakauchi H, KoefflerHP, Sanada M.
    • Journal Title

      Clin Cancer Res

      Volume: 16 Pages: 3825-3831

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mice lacking Dok-1, Dok-2, and Dok-3 succumb to aggressive histiocytic sarcoma.2010

    • Author(s)
      Mashima R, Honda K, Yang Y, Morita Y, Inoue A, Arimura S, Nishina H, Ema H, Nakauchi H, Seed B, Oda H, Yamanashi Y.
    • Journal Title

      Lab Invest

      Volume: 17 Pages: 271-5

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reprogramming adult hematopoietic cells.2010

    • Author(s)
      Kaneko S, Otsu M, Nakauchi H.
    • Journal Title

      Curr Opin Hematol

      Volume: 17 Pages: 271-275

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hair follicle stem cells provide a functional niche for melanocyte stem cells.2010

    • Author(s)
      Tanimura S, Tadokoro Y, Inomata K, Binh NT, Nishie W, Yamazaki S, Nakauchi H, Tanaka Y, McMillan JR, Sawamura D, Yancey K, ShimizuH, Nishimura EK.
    • Journal Title

      Cell Stem Cell

      Volume: 4 Pages: 177-87

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gain-of-function c-CBL mutations associated with uniparental disomy of 11q in myeloid neoplasms.2010

    • Author(s)
      Ogawa S, Sanada M, Shin LY, Suzuki T, Otsu M, Nakauchi H, Koeffler HP.
    • Journal Title

      Cell Cycle. 9(6)(In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Poised lineage specification in multipotential hematopoietic stem and progenitor cells by the polycomb protein Bmil.2010

    • Author(s)
      Oguro H, Yuan J, Ichikawa H, Ikawa T, Yamazaki S, Kawamoto H, Nakauchi H, Iwama A.
    • Journal Title

      Cell Stem Cell. 6(3)

      Pages: 279-86

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tissue type plasminogen activator regulates myeloid-cell dependent neoangiogenesis during tissue regeneration.2010

    • Author(s)
      Ohki M, Ohki Y, Ishihara M, Nishida C, Tashiro Y, Akiyama H, Komiyama H, Lund LR, Nitta A, Yamada K, Zhu Z, Ogawa H, Yagita H, Okumura K, Nakauchi H, Werb Z, Heissig B, Hattori K.
    • Journal Title

      Blood 6(3)(In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lnk regulates integrin alphaIIbbeta3 outside-in signaling in mouse platelets, leading to stabilization of thrombus development in vivo.2010

    • Author(s)
      Takizawa H, Nishimura S, Takayama N, Oda A, Nishikii H, Morita Y, Kakinuma S, Yamazaki S, Okamura S, Tamura N, Goto S, Sawaguchi A, Manabe I, Takatsu K, Nakauchi H, Takaki S, Eto K.
    • Journal Title

      J Clin Invest. 120

      Pages: 179-90

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Establishment of rat embryonic stem cell lines that can participate in germline chimerae at high efficiency.2010

    • Author(s)
      Hirabayashi M, Kato M, Kobayashi T, Sanbo M, Yagi T, Hochi S, Nakauchi H.
    • Journal Title

      Mol Reprod Dev. Nov 6(In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tumor suppression by phospholipase C-beta3 via SHP-1-mediated dephosphorylation of Stat52009

    • Author(s)
      Xiao W, Hong H, Kawakami Y, Kato Y, Wu D, Yasudo H, Kimura A, Kubagawa H, Bertoli LF, Davis RS, Chau LA, Madrenas J, Hsia CC, Xenocostas A, Kipps TJ, Hennighausen L, Iwama A, Nakauchi H, Kawakami T
    • Journal Title

      Cancer Cell

      Volume: 16 Pages: 161-71

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gain-of-function of mutated C-CBL tumour suppressor in myeloid neoplasms2009

    • Author(s)
      Sanada M, Suzuki T, Shih LY, Otsu M, Kato M, Yamazaki S, Tamura A, Honda H, Sakata-Yanagimoto M, Kumano K, Oda H, Yamagata T, Takita J, Gotoh N, Nakazaki K, Kawamata N, Onodera M, Nobuyoshi M, Hayashi Y, Harada H, Kurokawa M, Chiba S, Mori H, Ozawa K, Omine M, Hirai H, Nakauchi H, Koeffler HP, Ogawa S
    • Journal Title

      Nature

      Volume: 460 Pages: 904-8

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Definitive proof for direct reprogramming of hematopoietic cells to pluripotency2009

    • Author(s)
      Okabe M, Otsu M, Ahn DH, Kobayashi T, Wakiyama Y, Morita Y, Onodera M, Eto K, Ema H, Nakauchi H
    • Journal Title

      Blood

      Volume: 114 Pages: 1764-7

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Insights into signaling and function of hematopoietic stem cells at the single-cell level2009

    • Author(s)
      Yamazaki S, Nakauchi H
    • Journal Title

      Curr Opin Hemato

      Volume: 16 Pages: 255-8

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Stepwise development of hematopoietic stem cells from embryonic stem cells2009

    • Author(s)
      Matsumoto K, Isagawa T, Nishimura T, Ogaeri T, Eto K, Miyazaki S, Miyazaki J, Aburatani H, Nakauchi H, Ema H
    • Journal Title

      PLoS ONE

      Volume: 4

    • NAID

      120004898447

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The actin polymerization regulator WAVE2 is required for early bone marrow repopulation by hematopoietic stem cells2009

    • Author(s)
      Ogaeri T, Eto K, Otsu M, Ema H, Nakauchi H
    • Journal Title

      Stem Cells

      Volume: 27 Pages: 1120-1129

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] TGF-b induces hibernation of hematopoietic stem cells in the bone marrow niche2009

    • Author(s)
      Yamazaki S, Iwama A, Takayanagi S, Eto K, Ema H, Nakauchi H
    • Journal Title

      Blood

      Volume: 113 Pages: 1250-1256

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cardiac mast cells cause atrial fibrillation through PDGF-A-mediated fibrosis in pressure-overloaded mouse hearts.2009

    • Author(s)
      Liao CH, Akazawa H, Tamagawa M, Ito K, Yasuda N, Kudo Y, Yamamoto R, Ozasa Y, Fujimoto M, Wang P, Nakauchi H, Nakaya H, Komuro I.
    • Journal Title

      J Clin Invest. 120

      Pages: 242-53

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ex vivo expansion of human hematopoietic stem cells by a small-molecule agonist of c-MPL.2009

    • Author(s)
      Nishino T, Miyaji K, Ishiwata N, Arai K, Yui M, Asai Y, Nakauchi H, Iwama A.
    • Journal Title

      Exp Hematol. 37

      Pages: 1364-77

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of mesenchymal stem cells derived form arterial, venous, and Wharton's jelly explants of human umbilical cord2009

    • Author(s)
      Ishige I, Nagamura-Inoue T, Honda MJ, Harnprasopwat R, Kido M, Sugimoto M, Nakauchi H, Tojo A.
    • Journal Title

      Int J Hematol. 90

      Pages: 261-69

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tumor suppression by phospholipase C-beta3 via SHP-1-mediated dephosphorylation of Stat5.2009

    • Author(s)
      Xiao W, Hong H, Kawakami Y, Kato Y, Wu D, Yasudo H, Kimura A, Kubagawa H, Bertoli LF, Davis RS, Chau LA, Madrenas J, Hsia CC, Xenocostas A, Kipps TJ, Hennighausen L, Iwama A, Nakauchi H, Kawakami T.
    • Journal Title

      Cancer Cell. 16

      Pages: 161-71

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gain-of-function of mutated C-CBL tumour suppressor in myeloid neoplasms.2009

    • Author(s)
      Sanada M, Suzuki T, Shih LY, Otsu M, Kato M, Yamazaki S, Tamura A, Honda H, Sakata-Yanagimoto M, Kumano K, Oda H, Yamagata T, Takita J, Gotoh N, Nakazaki K, Kawamata N, Onodera M, Nobuyoshi M, Hayashi Y, Harada H, Kurokawa M, Chiba S, Mori H, Ozawa K, Omine M, Hirai H, Nakauchi H, Koeffler HP, Ogawa S.
    • Journal Title

      Nature 460

      Pages: 904-8

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Definitive proof for direct reprogramming of hematopoietic cells to pluripotency.2009

    • Author(s)
      Okabe M, Otsu M, Ahn DH, Kobayashi T, Wakiyama Y, Morita Y, Onodera M, Eto K, Ema H, Nakauchi H.
    • Journal Title

      Blood 114

      Pages: 1764-7

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Insights into signaling and function of hematopoietic stem cells at the single-cell level.2009

    • Author(s)
      Yamazaki S, Nakauchi H.
    • Journal Title

      Curr Opin Hematol. 16

      Pages: 255-8

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stepwise development of hematopoietic stem cells from embryonic stem cells.2009

    • Author(s)
      Matsumoto K, Isagawa T, Nishimura T, Ogaeri T, Eto K, Miyazaki S, Miyazaki J, Aburatani H, Nakauchi H, Ema H
    • Journal Title

      PLoS ONE. 4

    • NAID

      120004898447

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] T cell growth control using hapten-specific antibody/interleukin-2 receptor chimera.2009

    • Author(s)
      Sogo T, Kawahara M, Ueda H, Otsu M, Onodera M, Nakauchi H, Nagamune T.
    • Journal Title

      Cytokine 46

      Pages: 127-36

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A rapid and efficient strategy to generate allele-specific anti-HLA monoclonal antibodies.2009

    • Author(s)
      Yamazaki S, Suzuki N, Saito T, Ishii Y, Takiguchi M, Nakauchi H, Watanabe N.
    • Journal Title

      J Immunol Methods. 343

      Pages: 56-60

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The actin polymerization regulator WAVE2 is required for early bone marrow repopulation by hematopoietic stem cells.2009

    • Author(s)
      Ogaeri T, Eto K, Otsu M, Ema H, Nakauchi H.
    • Journal Title

      Stem Cells 27

      Pages: 1120-1129

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TGF-b induces hibernation of hematopoietic stem cells in the bone marrow niche.Blood.2009

    • Author(s)
      Yamazaki S, Iwama A, Takayanagi S, Eto K, Ema H, Nakauchi H.
    • Journal Title

      Blood 113

      Pages: 1250-56

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Generation of functional organs from pluripotent stem cells2011

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      Cold Spring Harbor Conferences Asia & ISSCR
    • Place of Presentation
      蘇州、中国(招待講演)
    • Year and Date
      2011-10-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] Generation of functional organs from iPS cells2011

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      12th International Congress on Reproductive Biomedicine & 7th International Congress on Stem Cell Biology and Technology
    • Place of Presentation
      Tehran, Iran(招待講演)
    • Year and Date
      2011-09-07
    • Related Report
      2011 Annual Research Report
  • [Presentation] Non-myelinating schwann cells in the mouse bone marrow niche maintain hematopoietic stem cell hibernation through TGF-beta signaling2011

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      Keystone Symposia
    • Place of Presentation
      USA
    • Year and Date
      2011-06-14
    • Related Report
      2011 Final Research Report
  • [Presentation] Non-myelinating Schwann cells in the mouse bone marrow niche maintain hematopoietic stem cell hibernation through TGF-b signaling2011

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      The Oklahoma Center for Adult Stem Cell Research (OCASCR)
    • Place of Presentation
      Oklahoma, USA(招待講演)
    • Year and Date
      2011-06-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] Generation of Rat Pancreas in Mouse : toward the next generation of regenerative medicine2011

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      ESHG Symposium
    • Place of Presentation
      Amsterdam, Holland(招待講演)
    • Year and Date
      2011-05-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] Non-myelinating Schwann cells in the mouse bone marrow niche maintain hematopoietic stem cell hibernation through TGF-b signaling2011

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      The Oklahoma Center for Adult Stem Cell Research(OCASCR)
    • Place of Presentation
      USA
    • Year and Date
      2011-05-20
    • Related Report
      2011 Final Research Report
  • [Presentation] Replicative senescence of hematopoietic stem cells after single cell transplantation2011

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      3rd Else Kroner-Fresenius Symposium on Molecular Mechanisms of Stem Cell Aging
    • Place of Presentation
      Ulm, Germany(招待講演)
    • Year and Date
      2011-05-20
    • Related Report
      2011 Annual Research Report
  • [Presentation] 3^<rd> Else Kroner-Fresenius Symposium on Molecular Mechanisms of Stem Cell Aging2011

    • Author(s)
      Hiromitsu Nakauchi
    • Place of Presentation
      Germany
    • Year and Date
      2011-04-01
    • Related Report
      2011 Final Research Report
  • [Presentation] Non-myelinating schwann cells in the mouse bone marrow niche maintain hematopoietic stem cell hibernation through TGF-beta signaling2011

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      Keystone Symposia
    • Place of Presentation
      Keystone, USA(招待講演)
    • Year and Date
      2011-04-01
    • Related Report
      2011 Annual Research Report
  • [Presentation] Molecular reguration of hematopoetic stemcell self-renewal and dormancy2009

    • Author(s)
      中内啓光
    • Organizer
      International PhD Prgram in Immunology, Cell Biology and Biochemistry 2008-2009 Lecture Course
    • Place of Presentation
      Switzerlamd, Bellinzona
    • Year and Date
      2009-05-28
    • Related Report
      2009 Annual Research Report
  • [Presentation] Heterogeneity and a hierarchy within the most primitive hematopoietic stem cell compartment2009

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      Symposium on Molecular Mechanisms of Adult Stem cell Aging
    • Place of Presentation
      Germany
    • Related Report
      2011 Final Research Report
  • [Presentation] Single-cell transplantation and clonal analysis of hematopoietic stem cells : Exploring heterogeneity and hierarchy2009

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      The 2009 ISEH(ISEH : International Society for Experimental Hematology) Donald Metclaf Lecture Award
    • Place of Presentation
      Greece
    • Related Report
      2011 Final Research Report
  • [Presentation] What's' blood donation'? A question from the future2009

    • Author(s)
      Hiromitsu Nakauchi
    • Organizer
      第71回日本血液学会総会
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report
  • [Presentation] Heterogeneity and a hierarchy within the most primitive hematopoietic stem cell compartment2009

    • Author(s)
      中内啓光
    • Organizer
      Symposium on Molecular Mechanisms of Adult Stem cell Aging.
    • Place of Presentation
      Reinsenburg, Germany
    • Related Report
      2009 Annual Research Report
  • [Presentation] A hierarchy within the most primitive hematopoietic stem cell compartment2009

    • Author(s)
      中内啓光
    • Organizer
      7th Catholic Int.Stem Cell Symposium in Seoul
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2009 Annual Research Report
  • [Presentation] SINGLE-CELL TRANSPLANTATION AND CLONAL ANALYSIS OF HEMATOPOIETIC STEM CELLS : EXPLORING HETEROGENEITY AND HIERARCHY2009

    • Author(s)
      中内啓光
    • Organizer
      The 2009 ISEH Donald Metclaf Lecture Award
    • Place of Presentation
      Athens, Greece
    • Related Report
      2009 Annual Research Report
  • [Presentation] Generation of organs from pluripotent stem cells.2009

    • Author(s)
      中内啓光
    • Organizer
      Abcam Stem Cells 2009
    • Place of Presentation
      Antigua/Balbuda
    • Related Report
      2009 Annual Research Report
  • [Presentation] Three-year clinical follow-up of 5 patients treated with suicide gene modified donor lymphocyte infusion therapy in Japan2009

    • Author(s)
      金子新、Y.Ohkokshi、大津真、N.Nemoto、T.Nanmoku、Kazumi Suzukawa、Y.Hasegawa、H.Kojima、T.Fukushima、R.Sumazaki、小野寺雅史、Y.Harada、H.Sakamaki、M.Tsuchida、S.Kato、C.Bonini、C.Bordignon、S.Chiba、中内啓光、T.Nakasawa
    • Organizer
      第15回日本遺伝子治療学会
    • Place of Presentation
      大阪
    • Related Report
      2009 Annual Research Report
  • [Presentation] 血液細胞由来iPS細胞の樹立2009

    • Author(s)
      岡部基人
    • Organizer
      第27回日本ヒト細胞学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2009 Annual Research Report
  • [Presentation] What's 'blood donation?'A question from the future2009

    • Author(s)
      中内啓光
    • Organizer
      第71回日本血液学会学術総会
    • Place of Presentation
      京都
    • Related Report
      2009 Annual Research Report
  • [Presentation] tPA regulates bone marrow derived cell dependent neoangiogenesis during tissue regeneration2009

    • Author(s)
      Koichi Hattori(服部先生)、Makiko Ohki、Yuichi Ohki、Chiemi Nishida、Makoto Ishihara、Yoshihiko Tashiro、Ismael Gritli、中内啓光、Beate Heissig
    • Organizer
      第71回日本血液学会学術総会
    • Place of Presentation
      京都
    • Related Report
      2009 Annual Research Report
  • [Presentation] iPS細胞研究の進展と臨床応用への期待2009

    • Author(s)
      中内啓光
    • Organizer
      第9回日本再生医療学会総会
    • Place of Presentation
      広島
    • Related Report
      2009 Annual Research Report
  • [Patent(Industrial Property Rights)] 多能性幹細胞からの血液細胞分化に関する培養方法2011

    • Inventor(s)
      佐野進弥、江藤浩之、高山直也、中内啓光
    • Industrial Property Rights Holder
      東京大学、テルモ株式会社
    • Filing Date
      2011-09-09
    • Related Report
      2011 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 誘導型多能性幹細胞の製造方法2011

    • Inventor(s)
      中内啓光,大津真,高山直也,安東赫
    • Industrial Property Rights Holder
      東京大学
    • Filing Date
      2011-06-15
    • Related Report
      2011 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 誘導型多能性幹細胞の製造方法2011

    • Inventor(s)
      中内啓光, 大津真, 高山直也, 安東赫
    • Industrial Property Rights Holder
      東京大学
    • Filing Date
      2011-06-15
    • Related Report
      2011 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 多能性幹細胞からの血液細胞分化に関する培養方法2011

    • Inventor(s)
      佐野進弥、江藤浩之、高山直也、中内啓光
    • Industrial Property Rights Holder
      東京大学テルモ株式会社
    • Filing Date
      2011-09-09
    • Related Report
      2011 Annual Research Report
    • Overseas

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Published: 2009-04-01   Modified: 2016-04-21  

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