Elucidation of the mechanisms underlying maintenance of hematopoietic stem cell hibernation

• Project/Area Number: 21249059
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: The 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: ¥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.

Research Products

• [Journal Article] A Differentiation Checkpoint Limits Hematopoietic Stem Cell Self-Renewal in Response to DNA Damage (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Lethal myelofibrosis induced by Bmi1-deficient hematopoietic cells unveils a tumor suppressor function of the polycomb group genes (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Plasmin inhibitor reduces lymphoid tumor growth by suppressing matrixmetallproteinase-9 dependent CD11b+/F4/80+ myeloid cell recruitment (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Lethal myelofibrosis induced by Bmil-deficient hematopoietic cells unveils a tumor suppressor function of the polycomb group genes (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Nonmyelinating Schwann cells maintain hematopoietic stem cell hibernation in the bone marrow niche (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Homeostasis of hematopoietic stem cells regulated by the myeloproliferative disease associated-gene product Lnk/Sh2b3 via Bcl-xL (2011)
  • Author(s): Suzuki N, Yamazaki S, Ema H, Yamaguchi T, Nakauchi H, Takaki S.
  • Journal Title: Exp Hematol Volume: 40 Pages: 166-74
  • Peer Reviewed
• [Journal Article] Integrin-αvβ3 regulates thrombopoietin-mediated maintenance of hematopoietic stem cells (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Ex vivo expansion of human hematopoietic stem cells by garcinol, a potent inhibitor of histone acetyltransferase (2011)
  • Author(s): Nishino T, Wang C, Mochizuki-Kashio M, Osawa M, Nakauchi H, Iwama A.
  • Journal Title: PLoS One Volume: 6
  • Peer Reviewed
• [Journal Article] Frequent pathway mutations of splicing machinery in myelodysplasia (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Hair follicle stem cells provide a functional niche for melanocyte stem cells (2011)
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Development of defective and persistent sendai virus vector : a unique gene delivery/expression system ideal for cell reprogramming (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Ex vivo expansion of human hematopoietic stem cells by garcinol, a potent inhibitor of histone acetyltransferase (2011)
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Transient activation of c-MYC expression is critical for efficient platelet generation from human induced pluripotent stem cells (2010)
  • 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
  • Peer Reviewed
• [Journal Article] Reprogramming adult hematopoietic cells (2010)
  • Author(s): Kaneko S, Otsu M, Nakauchi H
  • Journal Title: Opin Hematol Volume: 17 Pages: 271-5
  • 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, Koeffler HP, Sanada M
  • Journal Title: Clin Cancer Res Volume: 16 Pages: 3825-31
  • 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/lymphoma (2010)
  • Author(s): Nakahata S, Yamazaki S, Nakauchi H, Morishita K.
  • Journal Title: Oncogene Volume: 29 Pages: 4157-69
  • 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: 1173-82
  • Peer Reviewed
• [Journal Article] FET family proto-oncogene Fus contributes to self-renewal of hematopoietic stem cells (2010)
  • 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
  • Peer Reviewed
• [Journal Article] Koeffler HP, 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
  • Journal Title: Cell Cycle Volume: 9 Pages: 1051-6
  • 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: 279-86
  • 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 Volume: 115 Pages: 4302-12
  • 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 Volume: 120 Pages: 179-90
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Rat transgenesis via embryonic stem cells electroporated with the Kusabira-orange gene (2010)
  • Author(s): Hirabayashi M, Kato M, Sanbo M, Kobayashi T, Hochi S, Nakauchi H.
  • Journal Title: Mol Reprod Dev Volume: 77 Pages: 474-474
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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)
  • 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
  • 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)
  • 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
  • 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)
  • 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 Volume: 16 Pages: 161-71
  • 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 Volume: 460 Pages: 904-8
  • 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 Volume: 114 Pages: 1764-7
  • 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 Hemato Volume: 16 Pages: 255-8
  • 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 Volume: 4
  • NAID: 120004898447
  • 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 Volume: 27 Pages: 1120-1129
  • Peer Reviewed
• [Journal Article] TGF-b induces hibernation of hematopoietic stem cells in the bone marrow niche (2009)
  • Author(s): Yamazaki S, Iwama A, Takayanagi S, Eto K, Ema H, Nakauchi H
  • Journal Title: Blood Volume: 113 Pages: 1250-1256
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Comparison of mesenchymal stem cells derived form arterial, venous, and Wharton's jelly explants of human umbilical cord (2009)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Presentation] Generation of functional organs from pluripotent stem cells (2011)
  • 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
• [Presentation] Generation of functional organs from iPS cells (2011)
  • 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
• [Presentation] Non-myelinating schwann cells in the mouse bone marrow niche maintain hematopoietic stem cell hibernation through TGF-beta signaling (2011)
  • Author(s): Hiromitsu Nakauchi
  • Organizer: Keystone Symposia
  • Place of Presentation: USA
  • Year and Date: 2011-06-14
• [Presentation] Non-myelinating Schwann cells in the mouse bone marrow niche maintain hematopoietic stem cell hibernation through TGF-b signaling (2011)
  • 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
• [Presentation] Generation of Rat Pancreas in Mouse : toward the next generation of regenerative medicine (2011)
  • Author(s): Hiromitsu Nakauchi
  • Organizer: ESHG Symposium
  • Place of Presentation: Amsterdam, Holland(招待講演)
  • Year and Date: 2011-05-29
• [Presentation] Non-myelinating Schwann cells in the mouse bone marrow niche maintain hematopoietic stem cell hibernation through TGF-b signaling (2011)
  • Author(s): Hiromitsu Nakauchi
  • Organizer: The Oklahoma Center for Adult Stem Cell Research(OCASCR)
  • Place of Presentation: USA
  • Year and Date: 2011-05-20
• [Presentation] Replicative senescence of hematopoietic stem cells after single cell transplantation (2011)
  • 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
• [Presentation] 3^<rd> Else Kroner-Fresenius Symposium on Molecular Mechanisms of Stem Cell Aging (2011)
  • Author(s): Hiromitsu Nakauchi
  • Place of Presentation: Germany
  • Year and Date: 2011-04-01
• [Presentation] Non-myelinating schwann cells in the mouse bone marrow niche maintain hematopoietic stem cell hibernation through TGF-beta signaling (2011)
  • Author(s): Hiromitsu Nakauchi
  • Organizer: Keystone Symposia
  • Place of Presentation: Keystone, USA(招待講演)
  • Year and Date: 2011-04-01
• [Presentation] Molecular reguration of hematopoetic stemcell self-renewal and dormancy (2009)
  • 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
• [Presentation] Heterogeneity and a hierarchy within the most primitive hematopoietic stem cell compartment (2009)
  • Author(s): Hiromitsu Nakauchi
  • Organizer: Symposium on Molecular Mechanisms of Adult Stem cell Aging
  • Place of Presentation: Germany
• [Presentation] Single-cell transplantation and clonal analysis of hematopoietic stem cells : Exploring heterogeneity and hierarchy (2009)
  • Author(s): Hiromitsu Nakauchi
  • Organizer: The 2009 ISEH(ISEH : International Society for Experimental Hematology) Donald Metclaf Lecture Award
  • Place of Presentation: Greece
• [Presentation] What's' blood donation'? A question from the future (2009)
  • Author(s): Hiromitsu Nakauchi
  • Organizer: 第71回日本血液学会総会
  • Place of Presentation: 京都
• [Presentation] Heterogeneity and a hierarchy within the most primitive hematopoietic stem cell compartment (2009)
  • Author(s): 中内啓光
  • Organizer: Symposium on Molecular Mechanisms of Adult Stem cell Aging.
  • Place of Presentation: Reinsenburg, Germany
• [Presentation] A hierarchy within the most primitive hematopoietic stem cell compartment (2009)
  • Author(s): 中内啓光
  • Organizer: 7th Catholic Int.Stem Cell Symposium in Seoul
  • Place of Presentation: Seoul, Korea
• [Presentation] SINGLE-CELL TRANSPLANTATION AND CLONAL ANALYSIS OF HEMATOPOIETIC STEM CELLS : EXPLORING HETEROGENEITY AND HIERARCHY (2009)
  • Author(s): 中内啓光
  • Organizer: The 2009 ISEH Donald Metclaf Lecture Award
  • Place of Presentation: Athens, Greece
• [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
• [Presentation] Three-year clinical follow-up of 5 patients treated with suicide gene modified donor lymphocyte infusion therapy in Japan (2009)
  • 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
• [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
• [Presentation] What's 'blood donation?'A question from the future (2009)
  • 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
• [Presentation] tPA regulates bone marrow derived cell dependent neoangiogenesis during tissue regeneration (2009)
  • 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
• [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
• [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
  • 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
  • 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
  • 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
  • Overseas