Activation of stem cells and neurogenesis in adult brains : their regulatory mechanism and visualization

2009 Fiscal Year Final Research Report

• Project/Area Number: 17GS0317
• Research Category: Grant-in-Aid for Creative Scientific Research
• Allocation Type: Single-year Grants
• Research Institution: Keio University
• Principal Investigator: OKANO Hideyuki Keio University, 医学部, 教授 (60160694)
• Co-Investigator(Kenkyū-buntansha): YUZAKI Michisuke 慶應義塾大学, 医学部, 教授 (40365226) ; MIYAWAKI Atsushi 独立行政法人理化学研究所, 細胞機能探索技術開発チーム, チームリーダー (80251445) ; YAMASHIMA Tetsumori 金沢大学, 大学院・医学研究科, 准教授 (60135077) ; SAWAMOTO Kazunobu 名古屋市立大学, 大学院・医学研究科, 教授 (90282350) ; ITOHARA Shigeyoshi 独立行政法人理化学研究所, 行動遺伝学技術開発チーム, チームリーダー (60252524)
• Project Period (FY): 2005 – 2009
• Keywords: 神経科学 / 発生・分化 / 細胞・組織 / 再生医学 / 動物

Research Abstract

The discovery of neurogenesis in adult mammalian brains showed the possible application of neural stem cells (NSCs) to regenerative medicine of the nervous system. In this study, we tried to elucidate the physiological functions of two proteins that we had identified as regulators of NSCs, namely the RNA-binding protein Musashi-1 and the sugar chain-binding secretory protein Galectin-1, in adult mammalian brains. We also established a transgenic mouse system ("Color Timer") for visualizing neurogenesis with fluorescence.

Research Products

• [Journal Article] "Color Timer" mice: visualization of neuronal differentiation with fluorescent proteins. (2010)
  • Author(s): Kanki H, Shimabukuro MK, Miyawaki A, Okano H
  • Journal Title: Mol. Brain
  • Peer Reviewed
• [Journal Article] Subventricular zone-derived neural progenitor cells migrate along a blood vessel scaffold toward the post-stroke striatum. (2010)
  • Author(s): Kojima T, Hirota Y, Ema M, Takahashi S, Miyoshi I, Okano H, Sawamoto K
  • Journal Title: Stem Cells 28 Pages: 545-54
  • Peer Reviewed
• [Journal Article] Transplantation of galectin-1-expressing human neural stem cells into the injured spinal cord of adult common marmosets. (2010)
  • Author(s): Yamane J, Nakamura M, Iwanami A, Sakaguchi M, Katoh H, Yamada M, Momoshima S, Miyao S, Ishii K, Tamaoki N, Nomura T, Okano HJ, Kanemura Y, Toyama Y, Okano H
  • Journal Title: J. Neurosci. Res 88 Pages: 1394-405
  • Peer Reviewed
• [Journal Article] Musashi1 as a marker of reactive astrocytes after transient focal brain ischemia. Neurosci. (2009)
  • Author(s): Oki K, Kaneko N, Kanki H, Imai T, Suzuki N, Sawamoto K, Okano H
  • Journal Title: Neurosci. Res. 66(4) Pages: 390-5
  • Peer Reviewed
• [Journal Article] 3'-Untranslated region of doublecortin mRNA is a binding target of the Musashi1 RNA-binding protein. (2009)
  • Author(s): Horisawa K, Imai T, Okano H, Yanagawa H.
  • Journal Title: FEBS Lett 583(14) Pages: 2429-2434
  • Peer Reviewed
• [Journal Article] Cell types to order: temporal specification of CNS stem cells. (2009)
  • Author(s): Okano H, Temple S
  • Journal Title: Current Opinion in Neurobiology 19 Pages: 112-119
  • Peer Reviewed
• [Journal Article] Notch signaling mediates the segmental specification of angioblasts in somites and their directed migration toward the dorsal aorta in avian embryos. (2008)
  • Author(s): Sato Y, Watanabe T, Saito D, Takahashi T, Yoshida S, Kohyama J, Ohata E, Okano H, Takahashi Y
  • Journal Title: Dev. Cell 14 Pages: 890-901
  • Peer Reviewed
• [Journal Article] Neural RNA-binding protein Musashi1 Inhibits Translation Initiation by Competing with eIF4G for PABP. (2008)
  • Author(s): Kawahara H, Imai T, Imataka H, Okano H
  • Journal Title: J. Cell Biol 181 Pages: 639-653
  • Peer Reviewed
• [Journal Article] Epigenetic regulation of neural cell differentiation plasticity in the adult mammalian brain. (2008)
  • Author(s): Kohyama J, Kojima T, Takatsuka E, Yamashita T, Namiki J, Hsieh J, Gage FH, Namihira M, Okano H, Sawamoto K, Nakashima K
  • Journal Title: Proc. Natl. Acad. Sci. U S A. 105(46) Pages: 18012-18017
  • Peer Reviewed
• [Journal Article] A practical device for pinpoint delivery of molecules into multiple neurons in culture. (2008)
  • Author(s): Hara C, Tateyama K, Akamatsu N, Imabayashi H, Karaki K, Okano H, Miyawaki A
  • Journal Title: Brain Cell Biology (Epub 2008 Apr 5)
  • Peer Reviewed
• [Journal Article] Musashi1 modulates mammary progenitor cell expansion through proliferin-mediated activation of the Wnt and Notch pathways. (2008)
  • Author(s): Wang X-Y, Yin Yuzhi, Yuan H, Sakamaki T, Okano H, Glazer RI
  • Journal Title: Mol. Cell. Biol. (Epub 2008 Mar 24)
  • Peer Reviewed
• [Journal Article] Ontogeny and Multipotency of Neural Crest-Derived Stem Cells in Bone Marrow, Dorsal Root Ganglia and Whisker Pad of Adult Rodents. (2008)
  • Author(s): Nagoshi N, Shibata S, Kubota Y, Nakamura M, Nagai Y, Satoh E, Okada Y, Mabchi Y, Katoh H, Okada S, Fukuda K, Suda T, Matsuzaki Y, Toyama Y, Okano H
  • Journal Title: Cell Stem Cell 2 Pages: 392-403
  • Peer Reviewed
• [Journal Article] Cell cycle-dependent nestin gene expression coordinated with the morphological alteration of embryonic cortical neural progenitor cells. (2008)
  • Author(s): Sunabori T, Tokunaga A, Nagai T, Sawamoto K, Miyawaki A, Matsuzaki Y, Miyata T, Okano H
  • Journal Title: J. Cell Sci 121 Pages: 1204-1212
  • Peer Reviewed
• [Journal Article] Isolation and characterization of dendritic cells from common marmosets for preclinical studies on cell therapy. (2008)
  • Author(s): Ohta S, Ueda Y, Yaguchi M, Matsuzaki Y, Nakamura M, Toyama Y, Tanioka N, Tamaoki, N, Nomura T, Okano H, Kawakami Y, Toda M.
  • Journal Title: Immunology 123 Pages: 566-574
  • Peer Reviewed
• [Journal Article] Accumulation of AMPA receptors in autophagosomes in neuronal axons lacking adaptor protein AP-4. (2008)
  • Author(s): Matsuda S, Miura E, Matsuda K, Kakegawa W, Kohda K, Watanabe M, Yuzaki M
  • Journal Title: Neuron 57(5) Pages: 730-745
  • Peer Reviewed
• [Journal Article] Visualizing spatiotemporal dynamics of multicellular cell-cycle progression. (2008)
  • Author(s): Sakaue-Sawano A, Kurokawa H, Morimura T, Hanyu A, Hama H, Osawa H, Kashiwagi S, Fukami K, Miyata T, Miyoshi H, Imamura T, Ogawa M, Masai H, Miyawaki A
  • Journal Title: Cell 132(3) Pages: 487-498
  • Peer Reviewed
• [Journal Article] Helicobacter Pylori Infection Induces Candidate Stem Cell Marker Musashi-1 in theHuman Gastric Epithelium. (2008)
  • Author(s): Murata H, Tsuji S, Tsujii M, Nakamura T, Fu HY, Eguchi H, Asahi K, Okano H, Kawano S, Hayashi N
  • Journal Title: Dig Dis Sci 53 Pages: 363-369
  • Peer Reviewed
• [Journal Article] Cyclin-dependent kinase 5 is required for neuroblast migration in the adult brain. (2007)
  • Author(s): Hirota Y, Oshima T, Iwasato T, Kulkarni AB, Mikoshiba K, Okano H, Sawamoto K.
  • Journal Title: J. Neurosci 27 Pages: 12829-12838
  • Peer Reviewed
• [Journal Article] Side population in human uterine myometrium displays phenotypic and functional characteristics of myometrial stem cells. (2007)
  • Author(s): Ono M, Maruyama T, Masuda H, Kajitani T, Nagashima T, Arase T, Ito M, Ohta K, Uchida H, Asada H, Yoshimura Y, Okano H, Matsuzaki Y.
  • Journal Title: Proc. Natl. Acad. Sci. USA 104 Pages: 18700-18705
  • Peer Reviewed
• [Journal Article] In Vivo tracing of neural tracts in the intact and injured spinal cord of marmosets by diffusion tensor tractography. (2007)
  • Author(s): Fujiyoshi K, Yamada M, Nakamura M, Yamane J, Kato H, Kitamura K, Kawai K, Okada S, Momoshima S, Toayama Y, Okano H
  • Journal Title: J. Neurosci 27 Pages: 11991-11998
  • Peer Reviewed
• [Journal Article] Sawamoto Kβ-catenin signaling promotes proliferation of progenitor cells in the adult mouse subventricular zone. (2007)
  • Author(s): Adachi K, Mirzadesh Z, Sakaguchi M, Yamashita T, Nikolcheva T, Gotoh Y, Peltz G, Gong L, Kawase T, Alvarez-Buylla A, Okano H
  • Journal Title: Stem Cells 25 Pages: 2827-2836
  • Peer Reviewed
• [Journal Article] Galectin-1 regulates neurogenesis in the subventricular zone and promotes functional recovery after stroke. (2007)
  • Author(s): Ishibashi S, Kuroiwa T, Sakaguchi M, Sun L, Kadoya T, Okano H, Mizusawa H.
  • Journal Title: Exp. Neurol. 207 Pages: 302-313
  • Peer Reviewed
• [Journal Article] Coordinated Expression of HuD and GAP-43 in Hippocampal Dentate Granule Cells During Developmental and Adult Plasticity. (2007)
  • Author(s): Bolognani F, Tanner DC, Nixon S, Okano HJ, Okano H, Perrone-Bizzozero NI.
  • Journal Title: Neurochem Res 32 Pages: 2142-2151
  • Peer Reviewed
• [Journal Article] Plasma as a scaffold for regeneration of neural precursor cells after transplantation into rats with spinal cord injury. (2007)
  • Author(s): Takenaga M, Ohta Y, Tokura Y, Hamaguchi A, Suzuki N, Nakamura M, Okano H, Igarashi R.
  • Journal Title: Cell Transplant 16 Pages: 57-65
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor promotes endogenous repair and functional recovery after spinal cord injury. (2007)
  • Author(s): Kitamuta K, Iwanami A, Nakamura M, Yamane J, Kota W, Suzuki Y, Miyakawa D, Shibata S, Funakoshi H, Miyatakae S, Coffin R, Nakamura T, Toyama Y, Okano H
  • Journal Title: J Neurosci Res 85 Pages: 2332-2342
  • Peer Reviewed
• [Journal Article] Impaired Motor Functions in Mice Lacking the RNA-binding Protein Hzf. (2007)
  • Author(s): Iijima T, Ogura H, Takatsuki K, Shigenori Kawahara S, Wakabayashi K, Nakayama D, Fujioka M, Kimura Y, Bernstein A, Okano HJ, Kirino Y, Okano H
  • Journal Title: Neurosci Res 58 Pages: 183-189
  • Peer Reviewed
• [Journal Article] EGF-signaling mediated by Gab1 is required for the spatiotemporally regulated proliferation of Olig2-expressing progenitors in the embryonic spinal cord. (2007)
  • Author(s): Hayakawa-Yano Y, Nishida K, Fukami S, Gotoh Y, Hirano T, Nakagawa T, Shimazaki T, Okano H
  • Journal Title: Stem Cells 25 Pages: 1410-1412
  • Peer Reviewed
• [Journal Article] Leptin suppresses ghrelin-induced activation of neuropeptide Y neurons in the arcuate nucleus via phosphatidylinositol 3-kinase-and phosphodiesterase 3-mediated pathway. (2007)
  • Author(s): Kohno D, Nakata M, Maekawa F, Fujiwara K, Maejima Y, Kuramochi M, Shimazaki T, Okano H, Onaka T, Yada T.
  • Journal Title: Endocrinology 148 Pages: 2251-2263
  • Peer Reviewed
• [Journal Article] Musashi-1 expression in postnatal mouse olfactory epithelium. (2007)
  • Author(s): Watanabe K, Kondo K, Takeuchi N, Okano H, Yamasoba T
  • Journal Title: Neuroreort 18 Pages: 641-644
  • Peer Reviewed
• [Journal Article] Establishment of three-dimensional culture of neural stem/progenitor cells in collagen Type-1 Gel. (2007)
  • Author(s): Watanabe K, Nakamura M, Okano H, Toyama Y
  • Journal Title: Restorative Neurology and Neuroscience 25 Pages: 109-117
  • Peer Reviewed
• [Journal Article] Expression of neural RNA binding protein, Musashi1 in pediatric brain tumors. (2007)
  • Author(s): Nakano A, Kanemura Y, Mori K, Kodama E, Yamamoto A, Sakamoto H, Nakamura Y, Okano H, Yamasaki M, Arita N.
  • Journal Title: Pediatric Neurosurgery 43 Pages: 279-283
  • Peer Reviewed
• [Journal Article] Ca2+ permeability of the channel pore is not essential for the delta2 glutamate receptor to regulate synaptic plasticity and motor coordination. (2007)
  • Author(s): Kakegawa W, Miyazaki T, Hirai H, Motohashi J, Mishina M, Watanabe M, Yuzaki M
  • Journal Title: J Physiol 579(Pt3) Pages: 729-35
  • Peer Reviewed
• [Journal Article] Two distinct stem cell lineages in murine bone marrow (2007)
  • Author(s): Koide Y, Morikawa S, Mabuchi Y, Muguruma Y, Hiratsu E, Hasegawa K, Kobayashi M, Ando K, Kinjo K, Okano H, Matsuzaki Y.
  • Journal Title: Stem Cells 25 Pages: 1213-1221
  • Peer Reviewed
• [Journal Article] Beta-catenin activation and epithelial-mesenchymal transition in the pathogenesis of pterygium. (2007)
  • Author(s): Kato N, Shimmura S, Kawakita T, Miyashita H, Ozawa Y, Yoshida S, Higa K, Okano H, Tsubota K.
  • Journal Title: Invest Ophthalmol Vis Sci 48 Pages: 1511-1517
  • Peer Reviewed
• [Journal Article] Electrical stimulation modulates fate determination of differentiating embryonic stem cells. (2007)
  • Author(s): Yamada M, Tanemura K, Ozawa M, Ohyama R, Kitamura N, Kawano M, Tan-Takeuchi K, Mizuno H, Okada S, Iwanami A, Nakamura M, Ishitsuka C, Nagai A, Miyawaki A, Takashima A, Ogawa M, Okano H, Kondoh T
  • Journal Title: Stem Cells 25 Pages: 562-570
  • Peer Reviewed
• [Journal Article] Augmented Therapeutic Efficacy of an Oncolytic Herpes Simplex Virus Type 1 Mutant Expressing ICP34. 5 Under the Transcriptional Control of musashi1 Promoter in the Treatment of Malignant Glioma. (2007)
  • Author(s): Kanai R, Tomita H, Hirose Y, Ohba S, Goldman S, Okano H, Kawase T, Yazaki T.
  • Journal Title: Hum Gene Ther 18 Pages: 63-73
  • Peer Reviewed
• [Journal Article] A carbohydrate-binding protein, Galectin-1, promotes proliferation of adult neural stem cells. (2006)
  • Author(s): Sakaguchi M, Shingo T, Shimazaki T, Okano HJ, Shiwa M, Ishibashi S, Oguro H, Ninomiya M, Kadoya T, Horie H, Shibuya A, Mizusawa H, Poirier F, Nakauchi H, Sawamoto K, Okano H
  • Journal Title: Proc Natl Acad Sci USA. 103(18) Pages: 7112-7117
  • Peer Reviewed
• [Journal Article] Implication of "Down syndrome cell adhesion molecule" in the hippocampal neurogenesis of ischemic monkeys. (2006)
  • Author(s): Yamashima T, Popivanova BK, Guo J, Kotani S, Wakayama T, Iseki S, Sawamoto K, Okano H, Fujii C, Mukaida N, Tonchev AB
  • Journal Title: Hippocampus 16(11) Pages: 924-935
  • Peer Reviewed
• [Journal Article] A selective Sema3A inhibitor enhances regenerative responses and functional recovery of the injured spinal cord. (2006)
  • Author(s): Kaneko S, Iwanami A, Nakamura M, Kishino A, Kikuchi K, Shibata S, Okano HJ, Ikegami T, Moriya A, Konishi O, Nakayama C, Kumagai K, Kimura T, Sato Y, Goshima Y, Taniguchi M, Ito M, He Z, Toyama Y, Okano H
  • Journal Title: Nat. Med 12(12) Pages: 1380-1389
  • Peer Reviewed
• [Journal Article] A fluorescent variant of a protein from the stony coral Montipora facilitates dual-color single-laser fluorescence cross-correlation spectroscopy. (2006)
  • Author(s): Kogure T, Karasawa S, Araki T, Saito K, Kinjo M, Miyawaki A
  • Journal Title: Nat. Biotechnol 24(5) Pages: 577-581
  • Peer Reviewed
• [Journal Article] Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury. (2006)
  • Author(s): Okada S, Nakamura M, Katoh H, Miyao T, Shimazaki T, Ishii K, Yamane J, Yoshimura A, Iwamoto Y, Toyama Y, Okano H
  • Journal Title: Nat Med 12(7) Pages: 829-834
  • Peer Reviewed
• [Journal Article] Subventricular zone-derived neuroblasts migrate and differentiate into mature neurons in the post-stroke adult striatum. (2006)
  • Author(s): Yamashita T, Ninomiya M, Hernandez Acosta P, Garcia-Verdugo JM, Sunabori T, Sakaguchi M, Adachi K, Kojima T, Hirota Y, Kawase T, Araki N, Abe K, Okano H, Sawamoto K
  • Journal Title: J. Neurosci 26(24) Pages: 6627-6636
  • Peer Reviewed
• [Presentation] Regeneration of the Damaged CNS with iPS Cells (2010)
  • Author(s): Okano, H.
  • Organizer: KEYSTONE SYMPOSIA-Stem Cell Differentiation and Dedifferentiation
  • Place of Presentation: Colorado, U.S.A.
  • Year and Date: 2010-02-18
• [Presentation] Neural differentiation and cell therapy using pluripotent stem cells (2008)
  • Author(s): Okano, H.
  • Organizer: 2nd Symposium on Brian and Mind Research in the Asia/Pacific (BMAP)
  • Place of Presentation: The Matrix, Biopolis, Singapore
  • Year and Date: 2008-09-03
• [Presentation] Neural Stem Cells: their involvement in adult neurogenesis and CNS-repair (2007)
  • Author(s): Okano, H.
  • Organizer: The 7th World Congress of the International Brain Research Organization (IBRO) Symposium
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2007-07-15
• [Presentation] Neural Stem Cells: their involvement in adult neurogenesis and CNS-repair (2007)
  • Author(s): Okano, H.
  • Organizer: Stem Cells and CNS Regeneration
  • Place of Presentation: Bosotn, U.S.A.
  • Year and Date: 2007-06-01
• [Book] Tissue Stem Cells; Biology & Applications (2006)
  • Author(s): Okano, H
  • Total Pages: 424
  • Publisher: Taylor & Francis Group