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Kazuko Koshiba

    Department of Life Sciences　Professor
    Research Center for Biomedical Engineering　Researcher
    Research Institute of Industrial Technology　Researcher
Last Updated :2024/04/23

Researcher Information

Alias Name

    KOSHIBA-TAKEUCHI Kazuko

Research funding number

  • 30467005

J-Global ID

Research Interests

  • 形態進化   再生   発生   心臓   

Research Areas

  • Life sciences / Developmental biology

Academic & Professional Experience

  • 2017/04 - Today  Toyo UniversityFaculty of Life Sciences, Department of Applied Biosciences教授
  • 2016/04 - 2017/03  Toyo UniversityFaculty of Life Sciences, Department of Applied Biosciences准教授
  • 2010/04 - 2016/03  The University of TokyoInstitute of Molecular and Cellular Biosciences講師
  • 2010/02 - 2010/03  The University of TokyoInstitute of Molecular and Cellular Biosciences助教
  • 2007/09 - 2010/01  Tokyo Institute of Technologyグローバルエッジ研究院山村フェロー博士研究員・東工大特別研究員・特別研究員(RPD)
  • 2006/10 - 2007/08  UCSFグラッドストーン研究所博士研究員
  • 2002/10 - 2006/09  トロント小児病院心循環器研究部門リサーチ・アソシエート
  • 1998/04 - 2002/09  Nara Institute of Science and TechnologyGraduate School of Biological Sciences教務職員
  • 1997/04 - 1998/03  The University of TokushimaFaculty of Engineering, Department of Biological Science and Technology未来開拓研究員
  • 1995/05 - 1997/03  ERATO吉里再生機構プロジェクト研究員

Education

  •        - 1995/04  東北大学大学院  理学研究科  生物学専攻博士課程
  •        - 1992/03  東北大学大学院  理学研究科  生物学専攻修士課程
  •        - 1990/03  Tohoku University  Faculty of Science  Department of Biology

Published Papers

MISC

Awards & Honors

  • 2010 日本動物学会奨励賞
     
    受賞者: 小柴 和子
  • 2007 公益信託山村富美記念女性科学研究者研究助成基金
     
    受賞者: 小柴 和子
  • 2002 上原記念生命科学財団 海外留学助成リサーチフェローシップ
     
    受賞者: 小柴 和子

Research Grants & Projects

  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2022/04 -2025/03 
    Author : 竹内 純; 小柴 和子; 井原 健介
  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2021/04 -2024/03 
    Author : 小柴 和子
     
    脊椎動物の心臓の形態は様々であり、魚類は1心房1心室、両生類は2心房1心室、ワニ目・鳥類・哺乳類は2心房2心室の心臓を有する。このような形態変化は2心房2心室の心臓をもつマウスの心臓発生においても認められ、心房と心室の区画ができた後に、心房中隔と心室中隔が形成されることにより、2心房2心室の心臓が形作られる。心室中隔の形成には転写因子Tbx5の左心室への局在が心臓の進化発生において重要であることが分かっており、心房中隔形成においても心房に極性をもって発現する因子の関与があるのではないかと考え、マウス心房で左右に極性をもって発現する因子をゼブラフィッシュ、肺魚、アフリカツメガエル、マウスで比較したところ、左心房へのPitx2の局在が心房中隔の形成と非常によく関連していることを見出した。そこで、Pitx2の極性をもった発現が、心房中隔形成および心臓機能に与える影響を明らかにするために、Pitx2を心臓全体に発現するマウスを作出し、形態解析および遺伝子発現解析を行った。Pitx2の過剰発現によって発現が上昇する因子のうち、表現型との関連が深いと考えられる因子に着目し、Pitx2による発現制御機構の詳細について解析を進めている。また、心臓は、拍動を担う作業心筋だけでなく、洞房結節といった特殊心筋や心臓線維芽細胞などのさまざまな細胞種によって構成され、それらの相互作用が心臓の形成、機能維持に重要である。そこで、Pitx2の過剰発現による影響を細胞種ごとに調べるための解析系を構築中である。
  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2019/04 -2022/03 
    Author : 渡邉 裕介; 小柴 和子; 中川 修; 浦崎 明宏; LAMRI LYNDA; 能丸 寛子; 原田 恭弘; 垣花 優希; 橋本 大輝; 劉 孟佳; 瀬谷 大貴; 田中 亨
     
    本研究は①「胸部大血管形成における内皮細胞発生・管腔構造形成の重要性と制御機構の解明」と、②「心室筋の異なる領域における転写制御機構と細胞運命の解明」を目的として転写抑制に機能するHeyファミリー因子に着目して研究を進めている。 ①について、本年度は胸部大血管形成における内皮細胞でのHey1遺伝子の重要性を明らかにするため、胸部大血管の由来となる胎生10.5日目胚での咽頭弓動脈の構造および遺伝子発現についても解析を進めた。その結果、内皮細胞でHey1遺伝子を欠損させたcKOマウスでは第4咽頭弓動脈の形成異常が生じ、動脈内皮細胞マーカーの発現が消失することを観察した。一方、cKOマウスの咽頭弓動脈での平滑筋細胞マーカーや神経堤細胞マーカーの発現は正常であった。前年度および今年度の結果から、内皮細胞で発現するHey1遺伝子の胸部大血管形成における重要性と転写制御機構の一端を明らかにした。本研究実績はJBC誌に投稿し受理された（Watanabe et al., 2021. 筆頭および責任著者）。 ②について、本年度は胎生期心室筋で発現するHey2遺伝子の機能解析を行った。右心室から心室間領域にかけてHey2遺伝子を欠損させたcKOマウスでは、全身Hey2遺伝子欠損と同様に心室中隔欠損、三尖弁形成異常、右心室低形成を生じた。cKOマウス右心室では転写抑制に機能するTbx2の発現が異所的に誘導され、その下流遺伝子であるMycn発現が減少していた。さらに細胞増殖も低下していた。以上から、Hey2-Tbx2-Mycnの転写抑制カスケードが右心室形成に必須であることが示された。本研究実績はDev Growth Differ誌に投稿し受理された（Seya et al., 2021. 共責任著者）。
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2018/04 -2021/03 
    Author : Koshiba-Takeuchi Kazuko
     
    Teleost such as zebrafish have the unique outflow tract called as bulbus arteriosus, which is composed from smooth muscle and rich in elastin, whereas the outflow tract of many vertebrates is composed from myocardium. The previous study has indicated that the duplication and sub/neofunctionalization of elastin gene is critical for the formation of bulbus arteriosus. In this study, I focused on ltbp and fibulin which promote the elastin synthesis, and found that the expression patterns of these genes were identical to that of elastinb gene in zebrafish heart development. Moreover, I revealed that the expressions of these elastin-related genes in the outflow tract are regulated by TGFbeta signaling.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2014/04 -2017/03 
    Author : Koshiba-Takeuchi Kazuko; MORIYAMA Yuuta; KASUGAI Takashi; YOSHIDA Masa-aki
     
    Cephalopod has three hearts; one is a systemic heart and others are branchial hearts. The systemic heart has a role to circulate blood flow to the entire body, while the branchial heart is an organ to send the blood specifically to the branchial. Although a unique circulation system of cephalopod is well known, the developmental process of these hearts in the cephalopod embryo is still unclear. In this study, the squid homologues to cardiac specific transcription factor genes in vertebrate were isolated to examine the expression patterns in heart development by using Idiosepius paradoxus embryos. The cardiac transcription factor genes were specifically expressed in the presumptive cardiac region in squid embryo suggesting that both systemic and branchial hearts would be derived from the same cardiac field.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2013/04 -2016/03 
    Author : Takeuchi Jun; KOSHIBA KAZUKO; SHIRAHIGE KATSUHIKO
     
    For mammalian heart regeneration or repair, we have reported about two factors during heart regeneration to JMCC (Morita et al., 2016a) and DGD (Nakamura et al., 2016). Sall1 which plays as a key factor for cardiac induction (Morita et al., JMCC 2016a) is also re-activated during heart regeneration (Morita et al., submitted 2016b). Baf60c has been identified as a key factor for cardiac formation (Koshiba-Takeuchi et al., Etiology and Morphogenesis of Congenital Heart Disease 2016; Takeuchi & Bruneau. Nature 2009) and also functions for heart regeneration (Nakamura et al., DGD 2016). These results will open the regenerative mechanisms in several organs for the basic science and will give us supportive idea for the heart repair in human.
  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2011/04 -2012/03 
    Author : 小柴 和子
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2012 -2012 
    Author : TAKEUCHI Jun; TSUKAHARA Yuko; KOSHIBA Kazuko; SHIRAHIGE Katsuhiko
     
    Mammalian hearts have been limited their regenerative capacity, whereas fishes and amphibians keep high plasticity even in the adult. However, no factors have been reported as key factors for cardiac regeneration between mammalians and fishes. Recently, several epigenetic factors with specific roles in cardiogenesis have been reported. Especially, Brg1-BAF60c, main component in SWI/SNF chromatin remodelling complexes play as key factors for cardiomyocyte induction or differentiation (Takeuchi&Bruneau, Nature 2009; Takeuchi et al., Nature Commun2011). Interestingly, Baf60c expression in the ventricle heart was completelydisappeared by postnatal 7 days (P7D) after birth. This line is so consistent withheart regeneration capacity in mammals, reported by Porrello et al. (Science 2011), suggesting that epigenetic molecules might be profoundly associated with mammalian heart regenerative capacity.To address the questions whether cardiac-Baf core component, Baf60c, acts as anearly response factor during heart regeneration or not, two animal models (axolotls for regenerative animals and mice for limited regenerative animals) were utilized. Baf60c mRNA and its protein were strongly up-regulated within 12 hours after heart resection in both axolotl and neonatal (P2D) mice, and their expression were maintained in both animals during heart regeneration. Interestingly, postnatal 3 weeks-mouse heart with Baf60c viral infection after resection keeps its regeneration capacity. BAF-TG mice in 8 weeks-adult, which was generated for stable expression of Baf60c in cardiomyocytes in adults, protected fibrosis post myocardial infarction (MI), following that heart function was recovered by 4 weeks.In vivo ChIP analyses have revealed that chromatin conformation in viralinfected-heart and BAF-TG hearts in adult mice was dramatically arranged. Brg1 directly binds on several cardiac fetal genes’ promoters and regulates their expression levels in Baf60c dependent manner. Surprisingly, major cardiac fetal and angiogenesis gene promoters in the Baf60c-infected heart and BAF-TG heart in adults were still opened, accordingly with remodelling of histone H3K4 or H3K9 methylated-modification enzymes, DNA-methylated enzymes, HDACs and NurD components on these promoters.These data indicated that chromatin-histone conformation change should benecessary for heart regeneration. In this session, we would like to show genome-wide analyses for understanding the mechanism of chromatin-histone regulation in heartplasticity and heart failure.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2008 -2010 
    Author : KOSHIBA Kazuko
     
    In vertebrates the heart morphology is varied from fish to mammals relating their life style. This fact is well known, but the molecular mechanism that provides such differences between four-chambered animals and non-four-chambered animals is unclear. Non-crocodilian reptiles hold a unique place in the evolution of the heart, as their ventricular chambers are apparent intermediates between three-chambered heart and four-chambered heart. We studied Tbx5 expression pattern in the reptiles and found that a steep and correctly positioned Tbx5 gradient is important for ventricular septum formation. This findings generally support the concept that altered expression of developmental regulators is an important aspect of morphological evolution.

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