Identification of human bone marrow niche to support HSCs
Project/Area Number |
24249056
|
Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Hematology
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Research Institution | The University of Tokyo |
Principal Investigator |
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Project Period (FY) |
2012-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥44,460,000 (Direct Cost: ¥34,200,000、Indirect Cost: ¥10,260,000)
Fiscal Year 2014: ¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000)
Fiscal Year 2013: ¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000)
Fiscal Year 2012: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
|
Keywords | 骨髄ニッチ / TGF-beta / 休眠状態 |
Outline of Final Research Achievements |
This project describes identification of human bone marrow niche to support HSCs. We hypothesized that identification of BM niche leads us to manipulate the function of human HSPCs in vivo and in vitro. Given that TGF-beta induces human HSPC hibernation, we analyzed the area where TGF is activated. Our result clearly showed that GFAP+ cells activate TGF and induce hibernation of human HSPCs in mouse BM. These findings were confirmed by the fact that nerve denervation reduces the number of human HSPCs in human BM. Furthermore, We first report suggesting an association between neural and hematopoietic systems.In this paper, we first described an innovative strategy to generate large numbers of HSCs from pluripotent stem cells. More specifically, we established in vivo differentiation system generating fully functional HSCs from mouse induced pluripotent stem cells. Using this system, we also succeeded in generating human HSCs from human iPSCs.
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Report
(4 results)
Research Products
(69 results)
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[Journal Article] Effect of donor chimerism to reduce the level of glycosaminoglycans following bone marrow transplantation in a murine model of mucopolysaccharidosis type II2015
Author(s)
Yokoi K, Akiyama K, Kaneshiro E, Higuchi T, Shimada Y, Kobayashi H, Akiyama M, Otsu M, Nakauchi H, Ohashi T, Ida H
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Journal Title
J Inherit Metab Dis
Volume: 38
Pages: 333-340
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Screening of Drugs to Treat 8p11 Myeloproliferative Syndrome Using Patient-Derived Induced Pluripotent Stem Cells with Fusion Gene CEP110-FGFR1.2015
Author(s)
Yamamoto S, Otsu M, Matsuzaka E, Konishi C, Takagi H, Hanada S, Mochizuki S, Nakauchi H, Imai K, Tsuji K, Ebihara Y
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Journal Title
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Inhibition of plasmin attenuates murine acute graft-versus-host disease mortality by suppressing the matrix metalloproteinase-9-dependent inflammatory cytokine storm and effector cell trafficking2015
Author(s)
A Sato, C Nishida, K Sato-Kusubata, M Ishihara, Y Tashiro, I Gritli, H Shimazu, S Munakata, H Yagita, K Okumura, Y Tsuda, Y Okada, A Tojo, H Nakauchi, S Takahashi, B Heissig and K Hattori
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Journal Title
Leukemia
Volume: 29
Pages: 145-156
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Impaired hematopoietic differentiation of RUNX1-mutated induced pluripotent stem cells derived from FPD/AML patients. Leukemia,2014
Author(s)
Sakurai M, Kunimoto H, Watanabe N, Fukuchi Y, Yuasa S, Yamazaki S, Nishimura T, Sadahira K, Fukuda K, Okano H, Nakauchi H, Morita Y, Matsumura I, Kudo K, Ito E, Ebihara Y, Tsuji K, Harada Y, Harada H, Okamoto S, Nakajima H
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Journal Title
Leukemia.
Volume: 28
Pages: 2344-2354
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Expandable megakaryocyte cell lines enable clinically applicable generation of platelets from human induced pluripotent stem cells.2014
Author(s)
Nakamura S, Takayama N, Hirata S, Seo H, Endo H, Ochi K, Fujita KI, Koike T, Harimoto KI, Dohda T, Watanabe A, Okita K, Takahashi N, Sawaguchi A, Yamanaka S, Nakauchi H, Nishimura S, Eto K.
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Journal Title
Cell Stem Cell
Volume: 14
Pages: 535-48
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The Tif1β-Hp1 system maintains transcriptional integrity of hematopoietic stem cells.2014
Author(s)
Miyagi S, Koide S, Saraya A, Wendt GR, Oshima M, Konuma T, Yamazaki S, Mochizuki-Kashio M, Nakajima-Takagi Y, Wang C, Chiba T, Kitabayashi I, Nakauchi H, Iwama A.
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Journal Title
Stem cell reports
Volume: 2
Pages: 145-52
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Stage-specific roles for Cxcr4 signaling in murine hematopoietic stem/progenitor cells in the process of bone marrow repopulation2014
Author(s)
Lai CY, Yamazaki S, Okabe M, Suzuki S, Maeyama Y, Iimura Y, Onodera M, Kakuta S, Iwakura Y, Nojima M, Otsu M, Nakauchi H.
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Journal Title
Stem Cells
Volume: -
Pages: 1929-42
DOI
Related Report
Peer Reviewed
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[Journal Article] Down syndrome-associated haematopoiesis abnormalities created by chromosome transfer and genome editing technologies.2014
Author(s)
Kazuki Y, Yakura Y, Abe S, Osaki M, Kajitani N, Kazuki K, Takehara S, Honma K, Suemori H, Yamazaki S, Sakuma T, Toki T, Shimizu R, Nakauchi H, Yamamoto T, Oshimura M
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Journal Title
Sci Rep
Volume: 4
Pages: 6136-6136
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Gene targeting study reveals unexpected expression of brain-expressed X-linked 2 in endocrine and tissue stem/progenitor cells in mice.2014
Author(s)
Keiichi Ito, Satoshi Yamazaki, Ryo Yamamoto, Yoko Tajima, Ayaka Yanagida, Toshihiro Kobayashi, Megumi Kato-Itoh, Shigeru Kakuta, Yoichiro Iwakura, Hiromitsu Nakauchi, Akihide Kamiya,
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Journal Title
J Biol Chem.
Volume: 289(43)
Pages: 29892-298911
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Generation of induced pluripotent stem cells derived from primary and secondary myelofibrosis patient samples.2014
Author(s)
Hosoi M, Kumano K, Taoka K, Arai S, Kataoka K, Ueda K, Kamikubo Y, Takayama N, Otsu M, Eto K, Nakauchi H, Kurokawa M
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Journal Title
Experimental Hematology
Volume: (in press)
Pages: 816-25
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] A Chemical Probe That Labels Human Pluripotent Stem Cells.2014
Author(s)
Hirata N, Nakagawa M, Fujibayashi Y, Yamauchi K, Murata A, Minami I, Tomioka M, Kondo T, Kuo TF, Endo H, Inoue H, Sato S, Ando S, Kawazoe Y, Aiba K, Nagata K, Kawase E, Chang YT, Suemori H, Eto K, Nakauchi H, Yamanaka S, Nakatsuji N, Ueda K, Uesugi M
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Journal Title
Cell Rep
Volume: 6
Pages: 1165-1174
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] The generation of induced pluripotent stem cells (iPSCs) from patients with infantile and late-onset types of Pompe disease and the effects of treatment with acid-α-glucosidase in Pompe's iPSCs.2014
Author(s)
Higuchi T, Kawagoe S, Otsu M, Shimada Y, Kobayashi H, Hirayama R, Eto K, Ida H, Ohashi T, Nakauchi H, Eto Y
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Journal Title
Mol Genet Metab
Volume: 112
Pages: 44-48
DOI
Related Report
Peer Reviewed
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[Journal Article] Homeodomain transcription factor meis1 is a critical regulator of adult bone marrow hematopoiesis2014
Author(s)
Ariki R, Morikawa S, Mabuchi Y, Suzuki S, Nakatake M, Yoshioka K, Hidano S, Nakauchi H, Matsuzaki Y, Nakamura T, Goitsuka R.
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Journal Title
PLOS ONE
Volume: 9
Pages: 87646-87646
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Enzyme augmentation therapy enhances the therapeutic efficacy of bone marrow transplantation in mucopolysaccharidosis type II mice.2014
Author(s)
Akiyama K, Shimada Y, Higuchi T, Ohtsu M, Nakauchi H, Kobayashi H, Fukuda T, Ida H, Eto Y, Crawford BE, Brown JR, Ohashi T
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Journal Title
Mol Genet Metab.
Volume: 111
Pages: 139-46
DOI
Related Report
Peer Reviewed
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[Journal Article] Generation of Col2a1-EGFP-iPS cells for monitoring chondrogenic differentiation.2014
Author(s)
Saito T, Yano F, Mori D, Ohba S, Hojo H, Otsu M, Eto K, Nakauchi H, Tanaka S, Chung UI, Kawaguchi H
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Journal Title
DOI
Related Report
Peer Reviewed
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[Journal Article] Immortalization of Erythroblasts by c-MYC and BCL-XL Enables Large-Scale Erythrocyte Production from Human Pluripotent Stem Cells2013
Author(s)
Hirose, S., N. Takayama, S. Nakamura, K. Nagasawa, K. Ochi, S. Hirata, S. Yamazaki, T. Yamaguchi, M. Otsu, S. Sano, N. Takahashi, A. Sawaguchi, M. Ito, T. Kato, H. Nakauchi, and K. Eto.
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Journal Title
Stem cell reports
Volume: 1
Pages: 499-508
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Profiling of microRNA in human and mouse ES and iPS cells reveals overlapping but distinct microRNA expression patterns2013
Author(s)
Razak SR, Ueno K, Takayama N, Nariai N, Nagasaki M, Saito R, Koso H, Lai CY, Murakami M, Tsuji K, Michiue T, Nakauchi H, Otsu M, Watanabe S.
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Journal Title
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Congenital amegakaryocytic thrombocytopenia iPS cells exhibit defective MPL-mediated signaling2013
Author(s)
Shinji Hirata, Naoya Takayama,Ryoko Jono-Ohnishi, Hiroshi Endo, Sou Nakamura, Takeaki Dohda, Masanori Nishi, Yuhei Hamazaki, Ei-ichi Ishii, Shin Kaneko, Makoto Otsu, Hiromitsu Nakauchi, Shinji Kunishima, and Koji Eto.
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Journal Title
The Journal of clinical investigation
Volume: 123
Pages: 3802-14
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Generation of transgenic mouse line expressing Kusabira Orange throughout body, including erythrocytes, by random segregation of provirus method.2013
Author(s)
Hamanaka S, Ooehara J, Morita Y, Ema H, Takahashi S, Miyawaki A, Otsu M, Yamaguchi T, Onodera M, Nakauchi H
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Journal Title
Biochemical and biophysical research communications
Volume: i435(4)
Pages: 586-591
DOI
Related Report
Peer Reviewed
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[Journal Article] Manipulation of hematopoietic stem cells for regenerative medicine2013
Author(s)
Nakajima-Takagi Y, Osawa M, Oshima M, Takagi H, Miyagi S, Endoh M, Endo TA, Takayama N, Eto K, Toyoda T, Koseki H, Nakauchi H, Iwama A.
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Journal Title
Blood
Volume: 121
Pages: 447-458
DOI
Related Report
Peer Reviewed
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[Journal Article] MT1-MMP plays a critical role in hematopoiesis by regulating HIF-mediated chemokine/cytokine gene transcription within niche cells2012
Author(s)
Chiemi Nishida, Kaori Kusubata, Yoshihiko Tashiro, Ismael Gritli, Aki Sato, Makiko Ohki-Koizumi, Yohei Morita, Makoto Nagano, Takeharu Sakamoto, Naohiko Koshikawa, Takahiro Kuchimaru, Shinae Kizaka-Kondoh, Motoharu Seiki, Hiromitsu Nakauchi, Beate Heissig, and Koichi Hattori.
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Journal Title
Blood.
Volume: 119
Pages: 5405-16
DOI
Related Report
Peer Reviewed
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[Journal Article] nhibition of PAI-1 induces neutrophil-driven neoangiogenesis and promotes tissue regeneration viaproduction of angiocrine factors in mice2012
Author(s)
Yoshihiko Tashiro, Chiemi Nishida, Kaori Sato-Kusubata, Makiko Ohki-Koizumi, Makoto Ishihara, Aki Sato, Ismael Gritli, Hiromitsu Komiyama, Yayoi Sato, Takashi Dan, Toshio Miyata, Ko Okumura, Yuichi Tomiki, Kazuhiro Sakamoto, Hiromitsu Nakauchi, Beate Heissig, and Koichi Hattori.
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Journal Title
blood
Volume: 119
Pages: 6382-6393
DOI
Related Report
Peer Reviewed
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[Journal Article] Bmi1 confers resistance to oxidative stress on hematopoietic stem cells.2012
Author(s)
Nakamura S, Oshima M, Yuan J, Saray a A, Miyagi S, Konuma T, Yamazaki S, Osawa M, Nakauchi H, Koseki H, Iwama A.
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Journal Title
DOI
Related Report
Peer Reviewed
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[Journal Article] Development of an all-in-one inducible lentiviral vector for gene specific analysis of reprogramming.2012
Author(s)
Yamaguchi T, Hamanaka S, Kamiya A, Okabe M, Kawarai M, Wakiyama Y, Umino A, Hayama T, Sato H, Lee YS, Kato-Itoh M, Masaki H, Kobayashi T, Yamazaki S, Nakauchi H.
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Journal Title
DOI
Related Report
Peer Reviewed
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[Journal Article] Rapid T-cell chimerism switch and memory T-cell expansion are associated with pre-engraftment immune reaction early after cord blood transplantation.2012
Author(s)
Matsuno N, Yamamoto H, Watanabe N, Uchida N, Ota H, Nishida A, Ikebe T, Ishiwata K, Nakano N, Tsuji M, Asano-Mori Y, Izutsu K, Masuoka K, Wake A, Yoneyama A, Nakauchi H, Taniguchi S.
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Journal Title
Br J Haematol
Volume: 160
Pages: 255-8
DOI
Related Report
Peer Reviewed
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[Presentation] The Stem Cell Niche2015
Author(s)
Hiromitsu Nakauchi
Organizer
Gordon Research Conference
Place of Presentation
Ventura Beach Marriott, Ventura, CA. US
Year and Date
2015-02-15 – 2015-02-20
Related Report
Invited
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