Okuno, Hironobu



School of Medicine, Department of Physiology (Shinanomachi)



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  • 小児期より見られる遺伝性疾患の病態解明や創薬研究をiPS細胞を介したアプローチで目指しています。


Research Areas 【 Display / hide

  • Cell biology

  • Cell biology

  • Developmental biology

  • General physiology

  • Human genetics

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Research Keywords 【 Display / hide

  • induced pluripotent stem cells

  • genetic disorder


Books 【 Display / hide

  • Derivation of induced pluripotent stem cells by retroviral gene transduction in mammalian species.

    Okuno Hironobu, SpringerLink, 2012.07

  • [Future prospect of regenerative medicine into cure of genetic diseases].

    Okuno Hironobu, 2010.08

Papers 【 Display / hide

  • CHARGE syndrome modeling using patient-iPSCs reveals defective migration of neural crest cells harboring CHD7 mutations

    Okuno, H. Renault Mihara, F. Ohta, S. Fukuda, K. Kurosawa, K. Akamatsu, W. Sanosaka, T. Kohyama, J. Hayashi, K. Nakajima, K. Takahashi, T. Wysocka, J. Kosaki, K. Okano, H.

    Elife  2017.11

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  2050-084X

     View Summary

    CHARGE syndrome is a disease in which organs including the heart, eyes and ears may not develop properly. The cells that form the tissues affected by CHARGE syndrome develop in embryos from precursor cells called neural crest cells. Individuals with CHARGE syndrome also have mutations in a gene called CHD7. However, it is difficult to examine how CHD7 mutations affect neural crest cells in embryos.
    In recent years, cell reprogramming techniques have made it possible to create induced pluripotent stem cells (iPSCs) from the specialized somatic cells found in the human body. These iPSCs can be developed into many different cell types, including neural crest cells.
    Okuno et al. created iPSCs from the skin cells of people with CHARGE syndrome, developed these cells into neural crest cells, and compared them with neural crest cells that were developed from the skin cells of people without CHARGE syndrome. The neural crest cells developed from people with CHARGE syndrome showed multiple abnormalities. For example, they were not able to move around correctly. This is an important observation because neural crest cells must move through tissues to form the various organs affected by CHARGE syndrome.
    Okuno et al. also observed changes in the activity of many genes other than CHD7 in the neural crest cells developed from CHARGE patients. Further research is now needed to find out which genes are the most important for restoring the normal activity of neural crest cells.

  • Changeability of the fully methylated status of the 15q11.2 region in induced pluripotent stem cells derived from a patient with Prader-Willi syndrome

    Okuno, H. Nakabayashi, K. Abe, K. Ando, T. Sanosaka, T. Kohyama, J. Akamatsu, W. Ohyama, M. Takahashi, T. Kosaki, K. Okano, H.

    Congenit Anom (Kyoto) 57 ( 4 ) 96 - 103 2017.07

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  1741-4520

     View Summary

    Prader-Will syndrome (PWS) is characterized by hyperphagia, growth hormone deficiency and central hypogonadism caused by the dysfunction of the hypothalamus. Patients with PWS present with methylation abnormalities of the PWS-imprinting control region in chromosome 15q11.2, subject to parent-of-origin-specific methylation and controlling the parent-of-origin-specific expression of other paternally expressed genes flanking the region. In theory, the reversal of hypermethylation in the hypothalamic cells could be a promising strategy for the treatment of PWS patients, since cardinal symptoms of PWS patients are correlated with dysfunction of the hypothalamus. The genome-wide methylation status dramatically changes during the reprograming of somatic cells into induced pluripotent stem cells (iPSCs) and during the in vitro culture of iPSCs. Here, we tested the methylation status of the chromosome 15q11.2 region in iPSCs from a PWS patient using pyrosequencing and a more detailed method of genome-wide DNA methylation profiling to reveal whether iPSCs with a partially unmethylated status for the chromosome 15q11.2 region exhibit global methylation aberrations. As a result, we were able to show that a fully methylated status for chromosome 15q11.2 in a PWS patient could be reversed to a partially unmethylated status in at least some of the PWS-iPSC lines. Genome-wide DNA methylation profiling revealed that the partial unmethylation occurred at differentially methylated regions located in chromosome 15q11.2, but not at other differentially methylated regions associated with genome imprinting. The present data potentially opens a door to cell-based therapy for PWS patients and, possibly, patients with other disorders associated with genomic imprinting.

  • Microduplication of Xq24 and Hartsfield syndrome with holoprosencephaly, ectrodactyly, and clefting.

    Okuno Hironobu

    Am J Med Genet  2012.08

    Joint Work

  • Interstitial microdeletion of 4p16.3: contribution of WHSC1 haploinsufficiency to the pathogenesis of developmental delay in Wolf-Hirschhorn syndrome.

    Okuno Hironobu

    Am J Med Genet  2010.04

    Research paper (scientific journal), Joint Work

Presentations 【 Display / hide

  • Modeling of human neural crest cell disease: CHARGE syndrome patient iPSC-derived neural crest cells exhibit abnormal migration

    Okuno Hironobu

    日本神経科学会, 2015.07, Oral Presentation(general)

  • CHARGE症候群患者iPS細胞由来神経堤細胞を用いた病態解析

    Okuno Hironobu

    第55回日本先天異常学会、第38回小児遺伝学会合同会議, 2015.07, Oral Presentation(general)

  • CHARGE症候群患者iPS細胞由来神経堤細胞を用いた 神経堤細胞の遊走障害モデルの作製およびその分子メカニズムの探索

    Okuno Hironobu

    第45回慶應ニューロサイエンス研究会, 2013.04, Poster (general)

Research Projects of Competitive Funds, etc. 【 Display / hide

  • Elucidation of the mechanism of methylation maintenance of imprinting region using iPS cells


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 奥野 博庸, Grant-in-Aid for Early-Career Scientists , Principal Investigator

  • iPS細胞を用いた神経堤症モデルの作製及び神経堤症に対する創薬を目指した病態解明



Courses Taught 【 Display / hide