Details of a Researcher - Okano, Hideyuki

Papers - Okano, Hideyuki

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神経系の発生・分化とRNA

Okano Hideyuki, Imai Takao

蛋白質・核酸・酵素　増刊号　RNAの細胞生物学 48 ( 4 ) 430-437 2003.03

Research paper (scientific journal), Joint Work

Stem Cells Expressing Matrix Metalloproteinase-13 mRNA Appear during Regression Reversal of Hepatic Cirrhosis

Watanabe Tetsu, Niioka Maki, Hozawa Shigenari, Sugioka Yoshihiko, Arai Masao, Maruyama Katsuya, Okano Hideyuki, Okazaki Isao

361 - 388 2003.02

This chapter describes a mechanism that underlies the degradation of newly formed fibrous bands in CCl<inf>4</inf>-induced liver fibrosis and cirrhosis and demonstrates that neural progenitor cells derived from hematopoietic stem cells express interstitial collagenase in the recovery phase of experimental cirrhosis. It also discusses the availability of hematopoietic stem cells for the treatment of human liver fibrosis or cirrhosis. The reversibility of liver fibrosis in patients with alcoholic cirrhosis and alcoholic fatty liver with fibrosis has been observed after alcohol abstinence. Histologically documented reversibility of liver fibrosis in alcoholic liver diseases was closely correlated with a decrease in serum fibrosis markers of type IV collagen. It is now generally accepted that reversibility of liver fibrosis or cirrhosis occurs under some conditions if the cause of liver damage is removed or adequately treated.

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神経幹細胞の分化制御機構

Matsumoto Arifumi, Okano Hideyuki

ファルマシア 39 ( 2 ) 108-112 2003.02

Research paper (scientific journal), Joint Work

脊髄損傷に対する再生医療—神経幹細胞移植を中心として

Kaneko Shinjirou, Nakamura Masaya, Iwanami Akio, Ogawa Yuuto, Okano Hiroyuki, Toyama Yoshiaki

脊椎脊髄ジャーナル 16 ( 2 ) 123-129 2003.02

Research paper (scientific journal), Joint Work

再生医療の現状と将来展望；＜臓器再生＞中枢神経系の再生医療

Kaneko Shinnjirou, Iwanami Akio, Nakamura Masaya, Ogawa Yuuto, Toyama Yoshiaki, Okano Hiroyuki

日本医師会雑誌 129 ( 3 ) 355-359 2003.02

Research paper (scientific journal), Joint Work

中枢神経系の再生医療

Kaneko Shinjirou, Iwanami Akio, Nakamura Masaya, Ogawa Yuuto, Toyama Yoshiaki, Okano Hideyuki

日本医師会雑誌 129 ( 3 ) 355-359 2003.02

Research paper (scientific journal), Joint Work

幹細胞を利用した中枢神経系の再生

Sunabori Takehiko, Okano Hideyuki

最新医学 58 ( 1 ) 102-107 2003.01

Research paper (scientific journal), Joint Work

Identification of a putative intestinal stem cell and early lineage marker; musashi-1

Potten Christopher S, Booth Catherine, Tudor Gregory L, Booth Dawn, Brady Gerard, Hurley Patricia, Ashton Gary, Clarke Robert, Sakakibara Shin-ichi, Okano Hideyuki

Differentiation 71 ( 1 ) 28-41 2003.01

Research paper (scientific journal), Joint Work

Candidate markers for stem and early progenitor cells, Musashi-1 and Hes1, are expressed in crypt base columnar cells of mouse small intestine

Kayahara Takahisa, Sawada Mitsutaka, Takaishi Shigeo, Fukui Hirokazu, Seno Hiroshi, Fukuzawa Hiroaki, Suzuki Katsumasa, Hiai Hiroshi, Kageyama Ryoichiro, Okano Hideyuki, Chiba Ttsutomu

FEBS letterers 535 ( 39085 ) 131-135 2003.01

Research paper (scientific journal), Joint Work

Regulatory mechanisms of neural stem cell and strategies for therapy

Okada Seiji, Okano Hideyuki

Nippon rinsho. Japanese journal of clinical medicine 61 ( 3 ) 449 - 456 2003

ISSN 0047-1852

Neural stem cells(NSCs) are multipotential progenitor cells that can generate neurons, astrocytes, and oligodendrocytes, the three major cell types in the central nervous system. Due to their self-renewal activities, NSCs can proliferate in an undifferentiated state in vitro, allowing them to be expanded mitotically and harvested in bulk. Recent advances in stem cell biology have led us to investigate methods for the regenerative manipulation of the damaged CNS. However, there is much that is still not known about regulatory mechanisms of the differentiation and self-renewal of NSCs. In this article, we review some of the basic notions regarding the extracellular factors and signal transduction cascades involved in the differentiation and maintenance of NSCs.

Neural stem cells as therapeutic agents for CNS injuries and disorders.

Okano Hideyuki

International Congress Series 1810 39088 2003

Research paper (scientific journal), Single Work

Transplantation of neural stem cells into the spinal cord after injury

Okano Hideyuki, Ogawa Yuto, Nakamura Masaya, Kaneko Shinjiro, Iwanami Akio, Toyama Yoshiaki

Seminars in cells & developmental biology 379 39090 2003

Research paper (scientific journal), Joint Work

Retinal Development and Regeneration

Ozawa Yoko, Oguchi Yoshihisa, Okano Hideyuki

Neuro-Ophthalmology Japan 20 ( 3 ) 272 - 280 2003

ISSN 0289-7024

One of the final goals of our research is the regaining of normal functions previously lost in damaged tissue. While it has long been believed regeneration of the central nervous system was absolutely impossible, scientists have recently made progress towards this goal. For the regeneration of damaged tissues, both morphological and functional reconstitutions are an indispensable process. As undifferentiated cells, have better survival rates in all types of environments as well as better competency with regard to extracellular signaling factors, we have tried to take advantage of these characteristics. We are trying to find methodologies that will let these cells recapitulate the developmental processes in order to regain the normal physiological functions of damaged tissues. Some of the candidate cells that can be utilized for retinal regeneration are retinal stem cells and embryonic stem cells. In this study, we describe a method for inducing these cells towards specific cell fates as well as their potential therapeutic application. We also describe the significance of investigating the effects of the microenvironment in damaged retina for the purpose of inducing neural retinal regeneration.

RNA regulation in nervous system development and differentiation

Okano Hideyuki, Imai Takao

Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme 48 ( 4 Suppl ) 430 - 437 2003

ISSN 0039-9450

Regenerative treatment of nervous system diseases

Matsumoto Arifumi, Okano Hideyuki

Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine 92 ( 12 ) 2426 - 2432 2003

ISSN 0021-5384

Differential expression of Pax6 and Ngn2 between pair-generated cortical neurons

Kawaguchi Ayano, Ogawa Masaharu, Saito Kanako, Matsuzaki Fumio, Okano Hideyuki, Miyata Takaki

Journal of Neuroscience Research 78 ( 6 ) 784 - 795 2004.12

ISSN 0360-4012

Progenitor cells that generate neuron pairs ("pair progenitor cells") are implicated in mammalian cortical development, and their division has been thought to be "symmetric." However, asymmetric growth of two sister neurons generated by the division of a pair progenitor cell would lead to more efficient generation of neuronal diversity in the cortex. To explore mechanisms by which pair progenitor cells provide neuronal diversity, we examined molecular differences between a pair of neurons generated in clonal-density culture. Time-course analysis for the acquisition of neuronal markers and the disappearance of Pax6 and Neurogenin2 (Ngn2) demonstrated that 1) these transcription factors are expressed transiently in some but not all young neurons and 2) some neuron pairs showed uneven/asymmetric expression of Pax6 (19.5%) or Ngn2 (23.8%), whereas other pairs were either symmetrically positive or negative. Asymmetric Pax6 distribution in neuron pairs was not associated with asymmetric distribution of Numb, which raises an intriguing possibility, that Pax6 asymmetry in neuron pairs is produced by an alternative mode of the cell autonomous mechanisms. Stage-dependent changes were noted in the pattern of Ngn2 retention in daughter neurons, reflecting qualitative changes in the pair progenitor population. We suggest that pair progenitor cells contribute to the generation of neuronal diversity through cell-intrinsic heterogeneity and asymmetric division. © 2004 Wiley-Liss, Inc.

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Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction

Kawada Hiroshi, Fujita Jun, Kinjo Kentaro, Matsuzaki Yumi, Tsuma Mitsuyo, Miyatake Hiroko, Muguruma Yukari, Tsuboi Kosuke, Itabashi Yuji, Ikeda Yasuo, Ogawa Satoshi, Okano Hideyuki, Hotta Tomomitsu, Ando Kiyoshi, Fukuda Keiichi

Blood 104 ( 12 ) 3581 - 3587 2004.12

ISSN 0006-4971

Bone marrow (BM) cells are reported to contribute to the process of regeneration following myocardial infarction. However, the responsible BM cells have not been fully identified. Here, we used 2 independent clonal studies to determine the origin of bone marrow (BM)-derived cardiomyocytes. First, we transplanted single CD34^- c-kit⁺Sca-1⁺ lineage^- side population (CD34^-KSL-SP) cells or whole BM cells from mice ubiquitously expressing enhanced green fluorescent protein (EGFP) into lethally irradiated mice, induced myocardial infarction (MI), and treated the animals with granulocyte colony-stimulating factor (G-CSF) to mobilize stem cells to the damaged myocardium. At 8 weeks after MI, from 100 specimens we counted only 3 EGFP⁺ actinin⁺ cells in myocardium of CD34^- KSL-SP cells in mice that received transplants, but more than 5000 EGFP⁺ actinin⁺ cells in whole BM cell in mice that received transplants, suggesting that most of EGFP⁺ actinin⁺ cells were derived from nonhematopoietic BM cells. Next, clonally purified nonhematopoietic mesenchymal stem cells (MSCs), cardiomyogenic (CMG) cells, that expressed EGFP in the cardiomyocyte-specific manner were transplanted directly into BM of lethally irradiated mice, MI was induced, and they were treated with G-CSF. EGFP⁺ actinin⁺ cells were observed in the ischemic myocardium, indicating that CMG cells had been mobilized and differentiated into cardiomyocytes. Together, these results suggest that the origin of the vast majority of BM-derived cardiomyocytes is MSCs. © 2004 by The American Society of Hematology.

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Transcriptional integration of cell polarity and positional identity specifies daughters cell-fates in asymmetric cell division

Arata, Yukinobu, Kouike, Hiroko, Okano, Hideyuki, Sawa, Hitoshi

ZOOLOGICAL SCIENCE 21 ( 12 ) 1280 - 1280 2004.12

Research paper (scientific journal), ISSN 0289-0003

Retinoic-acid-concentration-dependent acquisition of neural cell identity during in vitro differentiation of mouse embryonic stem cells

Okada Yohei, Shimazaki Takuya, Sobue Gen, Okano Hideyuki

Developmental Biology 275 ( 1 ) 124 - 142 2004.11

ISSN 0012-1606

Retinoic acid (RA) is one of the most important morphogens, and its embryonic distribution correlates with neural differentiation and positional specification in the developing central nervous system. To investigate the concentration-dependent effects of RA on neural differentiation of mouse embryonic stem cells (ES cells), we investigated the precise expression profiles of neural and regional specific genes by ES cells aggregated into embryoid bodies (EBs) exposed to various concentrations of RA or the BMP antagonist Noggin. RA promoted both neural differentiation and caudalization in a concentration-dependent manner, and the concentration of RA was found to regulate dorso-ventral identity, i.e., higher concentrations of RA induced a dorsal phenotype, and lower concentrations of RA induced a more ventral phenotype. The induction of the more ventral phenotype was due to the higher expression level of the N-terminus of sonic hedgehog protein (Shh-N) when treated with low concentration RA, as it was abrogated by an inhibitor of Shh signaling, cyclopamine. These findings suggest that the concentration of RA strictly and simultaneously regulates the neuralization and positional specification during differentiation of mouse ES cells and that it may be possible to use it to establish a strategy for controlling the identity of ES-cell-derived neural cells. © 2004 Elsevier Inc. All rights reserved.

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Drosophila deltex mediates suppressor of hairless-independent and late-endosomal activation of notch signaling

Hori Kazuya, Fostier Maggy, Ito Mikiko, Fuwa Takashi J., Go Masahiro J., Okano Hideyuki, Baron Martin, Matsuno Kenji

Development 131 ( 22 ) 5527 - 5537 2004.11

ISSN 0950-1991

Notch (N) signaling is an evolutionarily conserved mechanism that regulates many cell-fate decisions. deltex (dx) encodes an E3-ubiquitin ligase that binds to the intracellular domain of N and positively regulates N signaling. However, the precise mechanism of Dx action is unknown. Here, we found that Dx was required and sufficient to activate the expression of gene targets of the canonical Su(H)-dependent N signaling pathway. Although Dx required N and a cis-acting element that overlaps with the Su(H)-binding site, Dx activated a target enhancer of N signaling, the dorsoventral compartment boundary enhancer of vestigial (vgBE), in a manner that was independent of the Delta (DI)/Serrate (Ser) ligands- or Su(H). Dx caused N to be moved from the apical cell surface into the late-endosome, where it accumulated stably and co-localized with Dx. Consistent with this, the dx gene was required for the presence of N in the endocytic vesicles. Finally, blocking the N transportation from the plasma membrane to the late-endosome by a dominant-negative form of Rab5 inhibited the Dx-mediated activation of N signaling, suggesting that the accumulation of N in the late-endosome was required for the Dx-mediated Su(H)-independent N signaling.

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