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動物再生システム学研究室
Laboratory of Animal Regeneration Systemology

担当教員 : 乾 雅史専任准教授
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<研究略歴>

2006年 東京大学大学理学系研究科生物科学専攻博士課程修了
2006年-2012年 Padua大学Department of Medical Biotechnologies 博士研究員
2012年-2017年 国立研究開発法人国立成育医療研究センター研究所 システム発生・再生医学研究部 ゲノム機能研究室長

<主な担当科目>

動物生命科学、動物再生システム学、生命科学実験I

<ひとこと>

自然の不思議さに驚き(Wonder)を感じられると人生は豊かになります

教員データベースはこちら

研究室のホームページはこちら

研究室 : 第一校舎2号館4階404号室

研究テーマ

動物再生システム学研究室では動物の器官や組織の発生(形ができる過程)について研究しています。実験材料として動物(主にマウス)と哺乳類培養細胞を使い、筋肉や骨格の形成過程をモデルとして実験を行っています。

近年の発生研究や幹細胞研究の成果から様々な細胞種の分化の過程が明らかになりつつありますが、機能的な組織(例えば筋骨格系で言えば筋肉が力を生み出し、それが腱を通じて骨格を動かすために必要な結合)を作るにはこれら多種細胞が互いにコミュニケーションをとって正しい形を作る必要がありますが、その詳しいメカニズムは未解明です。

個体の発生の中で複雑な組織が再現性を持って形成されるためには細胞の分化を制御する転写因子や細胞間のシグナル伝達が重要な役割を持ちます。

我々はゲノム編集技術を用いて転写因子やシグナル伝達系関連因子の遺伝子改変マウスを作成したり、発生過程や成体から組織をサンプリングしてその形態や遺伝子発現を解析する、あるいは培養細胞を用いてシグナル伝達やタンパク質翻訳後修飾の生化学的な評価をする、といったアプローチで筋骨格組織形成の分子メカニズムを明らかにする事を目標としています。

研究室メンバー

修士2年 5名; 修士1年 2名; 学部4年 5名; 学部3年 8名

研究業績

2020

Lin28a/let-7 pathway modulates the Hox code via Polycomb regulation during axial patterning in vertebrates.

Tempei Sato, Kensuke Kataoka, Yoshiaki Ito, Shigetoshi Yokoyama, Masafumi Inui, Masaki Mori, Satoru Takahashi, Keiichi Akita, Shuji Takada, Hiroe Ueno-Kudoh, Hiroshi Asahara  

eLife 9 e53608 2020

 

Generation of a Quantitative Luciferase Reporter for Sox9 SUMOylation.

Hideka Saotome, Atsumi Ito, Atsushi Kubo, Masafumi Inui*

International journal of molecular sciences 21(4) 1274 2020

 

2019

Deletion of a Seminal Gene Cluster Reinforces a Crucial Role of SVS2 in Male Fertility

Shindo M, Inui M, Kang W, Tamano M, Tingwei C, Takada S, Hibino T, Yoshida M, Yoshida K, Okada H, Iwamoto T, Miyado K, Kawano N.

International Journal of Molecular Sciences 20(18) 4557, 2019

 

Comparative analysis demonstrates cell type-specific conservation of SOX9 targets between mouse and chicken.

Yamashita S, Kataoka K, Yamamoto H, Kato T, Hara S, Yamaguchi K, Renard-Guillet C, Katou Y, Shirahige K, Ochi H, Ogino H, Uchida T, Inui M, Takada S, Shigenobu S, Asahara H.

Scientific reports 9(1) 12560, 2019

 

Creation of CRISPR-based germline-genome-engineered mice without ex vivo handling of zygotes by i-GONAD.

Gurumurthy CB, Sato M, Nakamura A, Inui M, Kawano N, Islam MA, Ogiwara S, Takabayashi S, Matsuyama M, Nakagawa S, Miura H, Ohtsuka M.

Nature protocols 2019

 

Wwp2 maintains cartilage homeostasis through regulation of Adamts5.

Mokuda S, Nakamichi R, Matsuzaki T, Ito Y, Sato T, Miyata K, Inui M, Olmer M, Sugiyama E, Martin Lotz M, Asahara H.

Nature Communications 10:2429, 2019

 

<2018>

Dissecting the roles of miR-140 and its host gene.

Inui M, Mokuda S, Sato T, Tamano M, Takada S, Asahara H.

Nature Cell Biology 20:516-8, 2019

 

<2017>

Tendons and Ligaments: Connecting Developmental Biology to Musculoskeletal Disease Pathogenesis.

Asahara H, Inui M, Lotz MK

Journal of bone and mineral research : 32(9):1773-1782 2017

 

CRISPR/Cas9-mediated simultaneous knockout of Dmrt1 and Dmrt3 does not recapitulate the 46, XY gonadal dysgenesis observed in 9p24. 3 deletion patients.

Inui M, Tamano M, Kato T, Takada S

Biochemistry and Biophysics Reports 9 238-244 2017

 

<2016>

The p.R92W variant of <i>NR5A1/Nr5a1</i> induces testicular development of 46,XX gonads in humans, but not in mice: phenotypic comparison of human patients and mutation-induced mice.

Miyado M, Inui M, Igarashi M, Katoh-Fukui Y, Takasawa K, Hakoda A, Kanno J, Kashimada K, Miyado K, Tamano M, Ogata T, Takada S, Fukami M

Biology of sex differences 7 56 2016

 

Mohawk promotes the maintenance and regeneration of the outer annulus fibrosus of intervertebral discs.

Nakamichi R, Ito Y, Inui M, Onizuka N, Kayama T, Kataoka K, Suzuki H, Mori M, Inagawa M, Ichinose S, Lotz MK, Sakai D, Masuda K, Ozaki T, Asahara H

Nature communications 7 12503 2016

 

<2015>

Generation of mutant mice via the CRISPR/Cas9 system using FokI-dCas9.

Hara S, Tamano M, Yamashita S, Kato T, Saito T, Sakuma T, Yamamoto T, Inui M, Takada S

Scientific reports 5 11221 Jun 2015

 

Transcription factor Mohawk controls tenogenic differentiation of bone marrow mesenchymal stem cells in vitro and in vivo.

Otabe K, Nakahara H, Hasegawa A, Matsukawa T, Ayabe F, Onizuka N, Inui M, Takada S, Ito Y, Sekiya I, Muneta T, Lotz M, Asahara H

Journal of orthopaedic research : 33(1) 1-8 2015

 

<2014>

Rapid generation of mouse models with defined point mutations by the CRISPR/Cas9 system.

Inui M, Miyado M, Igarashi M, Tamano M, Kubo A, Yamashita S, Asahara H, Fukami M, Takada S

Scientific reports 4 5396 2014

 

<2013>

Production of Sry knockout mouse using TALEN via oocyte injection.

Kato T, Miyata K, Sonobe M, Yamashita S, Tamano M, Miura K, Kanai Y, Miyamoto S, Sakuma T, Yamamoto T, Inui M, Kikusui T, Asahara H, Takada S

Scientific reports 3 3136 2013

 

<2012以前>

Self-regulation of the head-inducing properties of the Spemann organizer.

Inui M, Montagner M, Ben-Zvi D, Martello G, Soligo S, Manfrin A, Aragona M, Enzo E, Zacchigna L, Zanconato F, Azzolin L, Dupont S, Cordenonsi M, Piccolo S

Proceedings of the National Academy of Sciences of the United States of America 109(38) 15354-15359 2012

 

Regulation of TGF-β signal transduction by mono- and deubiquitylation of Smads.

Dupont S, Inui M, Newfeld SJ

FEBS letters 586(14) 1913-1920 2012

 

 miRNAs and morphogen gradients.

Inui M, Montagner M, Piccolo S

Current opinion in cell biology 24(2) 194-201 2012

 

The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells.

Cordenonsi M, Zanconato F, Azzolin L, Forcato M, Rosato A, Frasson C, Inui M, Montagner M, Parenti AR, Poletti A, Daidone MG, Dupont S, Basso G, Bicciato S, Piccolo S

Cell 147(4) 759-772 2011

 

USP15 is a deubiquitylating enzyme for receptor-activated SMADs.

Inui M, Manfrin A, Mamidi A, Martello G, Morsut L, Soligo S, Enzo E, Moro S, Polo S, Dupont S, Cordenonsi M, Piccolo S

Nature cell biology 13(11) 1368-1375 2011

 

An in vitro reconstitution system for the assessment of chromatin protein fluidity during Xenopus development.

Aoki R, Inui M, Hayashi Y, Sedohara A, Okabayashi K, Ohnuma K, Murata M, Asashima M

Biochemical and biophysical research communications 400(2) 200-206 2010

 

MicroRNA control of signal transduction.

Inui M, Martello G, Piccolo S

Nature reviews. Molecular cell biology 11(4) 252-263 2010

 

FAM/USP9x, a deubiquitinating enzyme essential for TGFbeta signaling, controls Smad4 monoubiquitination.

Dupont S, Mamidi A, Cordenonsi M, Montagner M, Zacchigna L, Adorno M, Martello G, Stinchfield MJ, Soligo S, Morsut L, Inui M, Moro S, Modena N, Argenton F, Newfeld SJ, Piccolo S

Cell 136(1) 123-135 2009

 

Tbx6, Thylacine1, and E47 synergistically activate bowline expression in Xenopus somitogenesis.

Hitachi K, Kondow A, Danno H, Inui M, Uchiyama H, Asashima M

Developmental biology 313(2) 816-828 2008

 

MicroRNA control of Nodal signalling.

Martello G, Zacchigna L, Inui M, Montagner M, Adorno M, Mamidi A, Morsut L, Soligo S, Tran U, Dupont S, Cordenonsi M, Wessely O, Piccolo S

Nature 449(7159) 183-188 2007

 

TSC-box is essential for the nuclear localization and antiproliferative effect of XTSC-22.

Hashiguchi A, Hitachi K, Inui M, Okabayashi K, Asashima M

Development, growth & differentiation 49(3) 197-204 2007

 

A novel gene, BENI is required for the convergent extension during Xenopus laevis gastrulation.

Homma M, Inui M, Fukui A, Michiue T, Okabayashi K, Asashima M

Developmental biology 303(1) 270-280 2007

 

Xapelin and Xmsr are required for cardiovascular development in Xenopus laevis.

Inui M, Fukui A, Ito Y, Asashima M

Developmental biology 298(1) 188-200 2006

 

A novel gene, Ami is expressed in vascular tissue in Xenopus laevis.

Inui M, Asashima M

Gene expression patterns : GEP 6(6) 613-619 2006

 

Identification and characterization of Xenopus OMP25.

Inui M, Asashima M

Development, growth & differentiation 46(5) 405-412 2004

 

Axial protocadherin is a mediator of prenotochord cell sorting in Xenopus.

Kuroda H, Inui M, Sugimoto K, Hayata T, Asashima M

Developmental biology 244(2) 267-277 2002

 

Bacteriophage WO and virus-like particles in Wolbachia, an endosymbiont of arthropods.

Masui S, Kuroiwa H, Sasaki T, Inui M, Kuroiwa T, Ishikawa H.

Biochem Biophys Res Commun. 283(5):1099–104. 2001

 

<その他>

「ゲノム編集による遺伝子改変について」 乾雅史

上智大学生命倫理研究所紀要「生命と倫理」第5p27-35 20183

 

「胚のゲノム編集」 乾雅史

HORMONE FRONTIER IN GYNECOLOGY Vol.26 No.2 2019 p11-16

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