研究業績

小池研究室および研究メンバーの研究成果を掲載しています。主要な研究成果に加え、原著論文、総説等を年代順に紹介します。

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主要論文

Modeling human hepato-biliary-pancreatic organogenesis from the foregut-midgut boundary

Nature, 2019

ヒト多能性幹細胞から肝・胆・膵領域の形成過程を再現する多細胞オルガノイドモデルを構築しました。

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Engineering human hepato-biliary-pancreatic organoids from pluripotent stem cells

Nature Protocols, 2021

ヒト肝・胆・膵オルガノイドを構築する実験手法を体系化しました。

［論文を見る］

Macrophage subpopulation promotes skeletal muscle regeneration through HGF/MET signaling-mediated skeletal muscle stem cell proliferation

Aging Cell, 2025

加齢骨格筋におけるマクロファージと筋幹細胞の相互作用を解析し、HGF/METシグナルによる再生制御機構を明らかにしました。

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研究業績

*:corresponding author, #:equal contribution

原著論文

2026

Goto M, Kurosawa T*, Koike H, Kaji N, Manabe I, Mihara T, Chaen T, Oishi Y, Hori M. COX2+/PDGFRα+ fibroblasts selectively localize near bile ducts and interact with immune cells in early liver fibrosis. Physiol. Rep. 14 (10): e70938. 2026. https://doi.org/10.14814/phy2.70938

2025

Koike H*, Sugimura M, Ouchi R, Yoshimoto Y, Manabe I, Oishi Y*. Macrophage subpopulation promotes skeletal muscle regeneration through HGF/MET signaling-mediated skeletal muscle stem cell proliferation. Aging Cell. 24 (6): e70042. 2025. https://doi.org/10.1111/acel.70042

Honda A, Koike H, Dohi T, Toyohara E, Hayakawa S, Tobe K, Manabe I, Ogawa R, Oishi Y*. CD206+ macrophages facilitate wound healing through interactions with Gpnmbhi fibroblasts. EMBO Rep. 26 (14): pp.3679-3704. 2025. https://doi.org/10.1038/s44319-025-00496-4

2024

Oishi Y*,#, Koike H# (#:co-first authors), Kumagami N#, Nakagawa Y, Araki M, Taketomi Y, Miki Y, Matsuda S, Kim H, Matsuzaka T, Ozawa H, Shimano H, Murakami M, Manabe I. Macrophage SREBP1 regulates skeletal muscle regeneration. Front. Immunol. 14: 1251784. 2024. https://doi.org/10.3389/fimmu.2023.1251784

Otomo K, Omura T, Nozawa Y, Edwards SJ, Sato Y, Saito Y, Yagishita S, Uchida H, Watakabe Y, Naitou K, Yanai R, Sahara N, Takagi S, Katayama R, Iwata Y, Shiokawa T, Hayakawa Y, Otsuka K, Watanabe-Takano H, Haneda Y, Fukuhara S, Fujiwara M, Nii T, Meno C, Takeshita N, Yashiro K, Rosales Rocabado JM, Kaku M, Yamada T, Oishi Y, Koike H, Cheng Y, Sekine K, Koga JI, Sugiyama K, Kimura K, Karube F, Kim H, Manabe I, Nemoto T, Tainaka K, Hamada A, Brismar H, Susaki EA*. descSPIM: an affordable and easy-to-build light-sheet microscope optimized for tissue clearing techniques. Nat. Commun. 15 (1): 4941. 2024. https://doi.org/10.1038/s41467-024-49131-1

2023

Watanabe A, Koike H*, Kumagami N, Shimba S, Manabe I, Oishi Y*. Arntl deficiency in myeloid cells reduces neutrophil recruitment and delays skeletal muscle repair. Sci. Rep. 13 (1): 6747. 2023. https://doi.org/10.1038/s41598-023-33830-8

Matsuzaki T*, Kawano Y, Horikiri M, Shimokawa Y, Yamazaki T, Okuma N, Koike H, Kimura M, Kawamura R, Yoneyama Y, Furuichi Y, Hakuno F, Takahashi S, Nakabayashi S, Okamoto S, Nakauchi H, Taniguchi H, Takebe T*, Yoshikawa HY*. Preparation of mechanically patterned hydrogels for controlling the self-condensation of cells. STAR Protoc. 4 (3): 102471. 2023. https://doi.org/10.1016/j.xpro.2023.102471

2022

Yuzawa R, Koike H, Manabe I, Oishi Y*. VDR regulates simulated microgravity-induced atrophy in C2C12 myotubes. Sci. Rep. 12 (1): 1377. 2022. https://doi.org/10.1038/s41598-022-05354-0

Matsuzaki T*, Shimokawa Y, Koike H, Kimura M, Kawano Y, Okuma N, Kawamura R, Yoneyama Y, Furuichi Y, Hakuno F, Takahashi S, Nakabayashi S, Okamoto S, Nakauchi H, Taniguchi H, Takebe T*, Yoshikawa HY*. Mechanical guidance of self-condensation patterns of differentiating progeny. iScience. 25 (10): 105109, 2022. https://doi.org/10.1016/j.isci.2022.105109

Hayakawa S, Tamura A, Nikiforov N, Koike H, Kudo F, Cheng Y, Miyazaki T, Kubekina M, Kirichenko TV, Orekhov AN, Yui N, Manabe I*, Oishi Y*. Activated cholesterol metabolism is integral for innate macrophage responses by amplifying Myd88 signaling. JCI Insight. 7 (22): e138539. 2022. https://doi.org/10.1172/jci.insight.138539

2021

Koike H, Iwasawa K, Ouchi R, Maezawa M, Kimura M, Kodaka A, Nishii S, Thompson WL, Takebe T*, Engineering human hepato-biliary-pancreatic organoids from pluripotent stem cells. Nat. Protoc. 16 (2): pp.919-936, 2021. https://doi.org/10.1038/s41596-020-00441-w

Liu L, Koike H, Ono T, Hayashi S, Kudo F, Kaneda A, Kagechika H, Manabe I, Nakashima T, Oishi Y*. Identification of a novel KLF5-dependent program and drug development for skeletal muscle atrophy. Proc. Natl. Acad. Sci. U.S.A. 118 (35): e2102895118, 2021. https://doi.org/10.1073/pnas.2102895118

Shinozawa T, Kimura M, Cai Y, Saiki N, Yoneyama Y, Ouchi R, Koike H, Maezawa M, Zhang RR, Dunn A, Ferguson A, Togo S, Lewis K, Thompson W, Asai A, Takebe T*, High-Fidelity Drug Induced Liver Injury Screen Using Human PSC-derived Organoids. Gastroenterology. 160 (3): pp.831-846, 2021. https://doi.org/10.1053/j.gastro.2020.10.002

2020

Han L#, Chaturvedi P#, Kishimoto K#, Koike H# (#:co-first authors), Nasr T, Iwasawa K, Giesbrecht K, Witcher PC, Eicher A, Haines L, Lee Y, Shannon JM, Morimoto M, Wells JM, Takebe T, Zorn AM*, Single cell transcriptomics identifies a signaling network coordinating endoderm and mesoderm diversification during foregut organogenesis. Nat. Commun. 11 (1): 4158, 2020. https://doi.org/10.1038/s41467-020-17968-x

2019

Koike H, Iwasawa K, Ouchi R, Maezawa M, Giesbrecht K, Saiki N, Ferguson A, Kimura M, Thompson WL, Wells JM, Zorn AM, Takebe T*, Modeling human hepato-biliary-pancreatic organogenesis from the foregut-midgut boundary, Nature. 574 (7776): pp.112-116, 2019. https://doi.org/10.1038/s41586-019-1598-0

Ouchi R, Togo S, Kimura M, Shinozawa T, Koido M, Koike H, Thompson W, Karns RA, Mayhew CN, McGrath PS, McCauley HA, Zhang RR, Lewis K, Hakozaki S, Ferguson A, Saiki N, Yoneyama Y, Takeuchi I, Mabuchi Y, Akazawa C, Yoshikawa HY, Wells JM, Takebe T*. Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids. Cell Metab. 30 (2): pp.374-384, 2019. https://doi.org/10.1016/j.cmet.2019.05.007

2018

Ong J, Serra MP, Segal J, Cujba AM, Ng SS, Butler R, Millar V, Hatch S, Zimri S, Koike H, Chan K, Bonham A, Walk M, Voss T, Heaton N, Mitry R, Dhawan A, Ebner D, Danovi D, Nakauchi H, Rashid ST*. Imaging-Based Screen Identifies Laminin 411 as a Physiologically Relevant Niche Factor with Importance for i-Hep Applications. Stem Cell Rep. 10 (3): pp.693-702, 2018. https://doi.org/10.1016/j.stemcr.2018.01.025

2017

Koike H, Zhang RR, Ueno Y, Sekine K, Zheng YW, Takebe T*, Taniguchi H*. Nutritional modulation of mouse and human liver bud growth through a branched-amino acid metabolism. Development. 144 (6): pp.1018-1024, 2017. https://doi.org/10.1242/dev.143032

2015

Takebe T*, Enomura M, Yoshizawa E, Kimura M, Koike H, Ueno Y, Matsuzaki T, Yamazaki T, Toyohara T, Osafune K, Nakauchi H, Yoshikawa HY*, Taniguchi H. Vascularized and complex organ buds from diverse tissues via mesenchymal cell-driven condensation. Cell Stem Cell. 16 (5): pp.556-565, 2015. https://doi.org/10.1016/j.stem.2015.03.004

2014

Koike H, Ueno Y, Naito T, Shiina T, Nakata S, Ouchi R, Obana Y, Sekine K, Zheng YW, Takebe T, Isono K, Koseki H, Taniguchi H*, Ring1B Promotes Hepatic Stem/Progenitor Cell Expansion by Simultaneous Repression of Cdkn1a and Cdkn2a, Hepatology. 60 (1): pp.323-333, 2014. https://doi.org/10.1002/hep.27046

Koike H, Ouchi R, Ueno Y, Nakata S, Obana Y, Sekine K, Zheng YW, Takebe T, Isono K, Koseki H, Taniguchi H*. Polycomb group protein Ezh2 regulates hepatic progenitor cell proliferation and differentiation in murine embryonic liver. PLoS One. 9 (8): e104776. 2014. https://doi.org/10.1371/journal.pone.0104776

Takebe T*, Zhang R#, Koike H# (#:co-second authors), Kimura M, Yoshizawa E, Enomura M, Sekine K, Taniguchi H*, Generation of a vascularized and functional human liver from an iPSC-derived organ bud transplant. Nat. Protoc. 9 (2): pp.396-409. 2014. https://doi.org/10.1038/nprot.2014.020

Zhang R, Takebe T*, Sekine K, Koike H, Zheng YW, Taniguchi H*. Identification of proliferating human hepatic cells from human induced pluripotent stem cells. Transplant. Proc. 46 (4): pp.1201-1204. 2014. https://doi.org/10.1016/j.transproceed.2013.12.021

Zhang R, Takebe T*, Miyazaki L, Takayama M, Koike H, Kimura M, Enomura M, Zheng YW, Sekine K, Taniguchi H, Efficient Hepatic Differentiation of Human Induced Pluripotent Stem Cells in a Three-Dimensional Microscale Culture, Methods Mol. Biol. 1210: pp.131-141, 2014. https://doi.org/10.1007/978-1-4939-1435-7_10

2013

Takebe T*, Sekine K, Enomura M, Koike H, Kimura M, Ogaeri T, Zhang RR, Ueno Y, Zheng YW, Koike N, Aoyama S, Adachi Y, Taniguchi H*. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature. 499 (7459): pp.481-484, 2013. https://doi.org/10.1038/nature12271

2012

Koike H, Kubota K, Sekine K, Takebe T, Ouchi R, Zheng YW, Ueno Y, Tanigawa N, Taniguchi H*, Establishment of automated culture system for murine induced pluripotent stem cells. BMC Biotechnol. 12: 81, 2012. https://doi.org/10.1186/1472-6750-12-81

総説（英文）

Ouchi R*, Koike H*. Modeling human liver organ development and diseases with pluripotent stem cell-derived organoids. Front. Cell Dev. Biol. 11: 1133534 , 2023. https://doi.org/10.3389/fcell.2023.1133534

Koike H, Manabe I, Oishi Y*. Mechanisms of cooperative cell-cell interactions in skeletal muscle regeneration. Inflamm. Regen. 42 (1): 48, 2022. https://doi.org/10.1186/s41232-022-00234-6

Koike H, Takebe T*, Generating Mini-Organs in Culture, Curr. Pathobiol. Rep. 4 (2): pp.59-68, 2016 https://doi.org/10.1007/s40139-016-0101-y

総説（和文）

小池博之, 大石由美子. 骨格筋萎縮に対するビタミンA誘導体の機能評価. 実験医学. 40 (7): pp.1027-1031, 2022

小池博之, 大石由美子. 骨格筋組織再生を対象としたシングルセルRNA-seq解析. 医学のあゆみ. 276 (5): pp.443-447, 2021

小池博之, 武部貴則. 多能性幹細胞を用いたヒト肝・胆・膵システムの一括創出. 実験医学. 38 (4): pp.590-593, 2020

小池博之, 武部貴則. 臓器の芽を創出する革新的な培養手法を確立. 自動車技術, 69 (11): pp.108-109, 2015

大崎達哉, 福田淳二, 小池博之, 武部貴則. ヒトiPS細胞を用いた複雑臓器の成形加工と移植医療への応用. 実験医学. 33 (8): pp.1259-1265, 2015

谷口英樹, 小池博之. 膵がんにおけるがん幹細胞の特性解析. 実験医学. 29 (20): pp.3254-3261, 2011

小池博之, 中田晋, 谷口英樹. 膵癌. 臨床検査. 55 (5): pp.495-499, 2011. https://doi.org/10.11477/mf.1542102623

著書

Koike H, Rashid T, Takebe T*. Translational Medicine Molecular Pharmacology and Drug Discovery (Edited by Robert A. Meyers). (担当: 分担執筆, 範囲: Growing Mini-Organs from Stem Cells. pp.137-158). Wiley-VCH Verlag GmbH & Co. KGaA. 2016 (ISBN: 9783527336593). https://doi.org/10.1002/3527600906.mcb.201600017

Zhang R, Koike H, Takebe T*, Hyper bio assembler for 3D cellular systems (Edited by Arai T, Arai F, and Yamato M), (担当: 分担執筆, 範囲: The Visualization of Human Organogenesis from Stem Cells by Recapitulating Multicellular Interactions. pp.275-283), Springer Japan, 2015 (ISBN: 9784431552963). https://doi.org/10.1007/978-4-431-55297-0_17

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