Publications

Article & Review

2022

Enteral liquid ventilation oxygenates a hypoxic pig model

iScience | 13 February

We assessed the enteral ventilation approach in hypoxic porcine models under controlled mechanical ventilation.

Fujii T, Yoneyama Y, Kinebuchi A, Ozeki N, Maeda S, Saiki N, Fengshi Chen-Yoshikawa T.F., Date H, Nishiwaki K, Takebe T

En masse organoid phenotyping informs metabolic-associated genetic susceptibility to NASH

Cell | 27 October

We devised a pooled human organoid-panel of steatohepatitis to investigate the impact of metabolic status on genotype-phenotype association.

Kimura M, Iguchi T, Iwasawa K, Dunn A, Thompson W, Yoneyama Y, Chaturvedi P, Zorn A, Wintzinger M, Quattrocelli M, Watanabe-Chailland M, Zhu G, Fujimoto M, Kumbaji M, Kodaka A, Gindin Y, Chung C, Myers R, Subramanian G, Hwa V, Takebe T

Watch the video abstract

Mechanical guidance of self-condensation patterns of differentiating progeny

iScience | 27 September

We have developed a mechanically patterned hydrogel for controlling self-condensation process to generate multi-cellular organoids.

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 H

Cell membrane fluidity and ROS resistance define DMSO tolerance of cryopreserved synovial MSCs and HUVECs

Stem cell research & therapy | 03 May

This study aimed to identify the biological and physical factors involved in the differences in freeze–thaw tolerance between MSCs and HUVECs.

Mizuno M, Matsuzaki T, Ozeki N, Katano H, Koga H, Takebe T, Yoshikawa HY & Sekiya I

Eicosatetraynoic Acid and Butyrate Regulate Human Intestinal Organoid Mitochondrial and Extracellular Matrix Pathways Implicated in Crohn’s Disease Strictures

Inflammatory Bowel Diseases | 08 March

We developed a patient-specific human intestinal organoid (HIO) model system to test small molecule regulation of mitochondrial and wound-healing functions implicated in stricturing behavior.

Ingrid Jurickova et al

Narrative engineering of the liver

Current Opinion in Genetics & Development | August

Lee and Takebe discuss advancements in liver organoid technology through the lens of ‘narrative engineering’ in an attempt to synergize evolving understanding around molecular and cellular landscape governing hepatogenesis with engineering-inspired approaches for organoidgenesis in this review.

Inkyu S Lee, Takanori Takebe

Correction of a Factor VIII genomic inversion with designer-recombinases

Nature Communications | 20 January

In this work, Lansing et al. present designer-recombinases as an efficient and specific means towards treatment of monogenic diseases caused by large gene inversions.

Lansing F, Mukhametzyanova L, Rojo-Romanos T. et al.

2021

Isolation and Characterization of Tissue Resident CD29-Positive Progenitor Cells in Livestock to Generate a Three-Dimensional Meat

Cells | 21 September

Naraoka et al. screened 246 cell-surface antibodies by fluorescence-activated cell sorting for their capacity to form colonies and their suitability to construct spheroid “meat buds”.

Naraoka Y, Mabuchi Y, Yoneyama Y, Suto EG, Hisamatsu D, Ikeda M, Ito R, Nakamura T, Takebe T, Akazawa C

Synthesis and application of POLYseq for profiling human liver organoids

STAR Protocols | 24 December

Dunn et al. updated the protocol for POLYseq using inexpensive, commercially available reagents.

Dunn A, Cai Y, Iwasawa K, Kimura M, Takebe T

Self-organized yolk sac-like organoids allow for scalable generation of multipotent hematopoietic progenitor cells from human induced pluripotent stem cells

bioRxiv

Tamaoki et al. showed that hiPSCs co-cultured with various types of stromal cells as spheroids self-organize into yolk sac-like organoids without the addition of exogenous factors.

Tamaoki N, Siebert S, Maeda T, Ngoc-H Ha, Good M L, Huang Y, Vodnala S K, Haro-Mora J J, Uchida N, Tisdale J F, Sweeney C L, Choi U, Brault J, Koontz S, Malech H L, Yamazaki Y, Isonaka R, Goldstein D S, Kimura M, Takebe T, Zou J, Stroncek D F, Robey P G, Kruhlak M J, Restifo N P, Vizcardo R

POLYseq: A poly(β-amino ester)-based vector for multifunctional cellular barcoding

Stem Cell Reports | 26 August

Dunn et al. developed a novel poly(β-amino) ester labeling system synthesized with inexpensive, common reagents, termed POLYseq, capable of efficiently delivering fluorescent molecules or sample-distinguishing DNA barcodes through non-covalent binding enabling rapid creation of custom sample pools. Andrew Dunn, Yuqi Cai, Kentaro Iwasawa, Masaki Kimura, Takanori Takebe.

Mammalian enteral ventilation ameliorates respiratory failure

Med | 14 May

Okabe el al. showed the effectiveness of an enteral ventilation approach in attaining systemic oxygenation in both rodent and porcine models, inspired by organisms such as loaches that use intestinal air breathing.

Ryo Okabe, Toyofumi F. Chen-Yoshikawa, Yosuke Yoneyama. Eiji Kobayashi, Hiroshi Date, Takanori Takebe.

Selected as Cover Article

Highlighted in Med Viewpoint, NYTimes, Economist, Science, Smithsonian Magazine, NYPost, National Geographic, TrontoStar the others.

Watch the video

Common Genetic Variation in Humans Impacts In Vitro Susceptibility to SARS-CoV-2 Infection

Stem Cell Reports | 9 March

Dobrindt et al. applied human induced pluripotent stem cell (hiPSC)-based models and CRISPR engineering to explore the host genetics of SARS-CoV-2.

Dobrindt K, Hoagland DA, Seah C, Kassim B, O’Shea CP, Murphy A, Iskhakova M, Fernando MB, Powell SK, Deans PJM, Javidfar B, Peter C, Møller R, Uhl SA, Garcia MF, Kimura M, Iwasawa K, Crary JF, Kotton DN, Takebe T, Huckins LM, tenOever BR, Akbarian S, Brennand KJ

Modeling Human Bile Acid Transport and Synthesis in Stem Cell-Derived Hepatocytes with a Patient-Specific Mutation

Stem Cell Reports | 9 February

Hayashi el al. developed a human induced pluripotent stem cell-based model of isogenic BSEP-deficient hepatocytes in a Transwell culture system.

Hayashi H, Osaka S, Sakabe K, Fukami A, Kishimoto E, Aihara E, Sabu Y, Mizutani A, Kusuhara H, Naritaka N, Zhang W, Huppert SS, Sakabe M, Nakamura T, Hu YC, Mayhew C, Setchell K, Takebe T, Asai A

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

Nature Protocol | 11 January

Koike et al. describe a protocol for the continuous patterning of hepatic, biliary and pancreatic (HBP) structures from a 3D culture of human pluripotent stem cells (PSCs).

Koike H, Iwasawa K, Ouchi R, Maezawa M, Kimura M, Kodaka A, Nishii S, Thompson WL, Takebe T

Simultaneous Zn2+ tracking in multiple organelles using super-resolution morphology-correlated organelle identification in living cells

Nature Communications | 4 January

Fang et al. developed a new turn-on Zn2+ fluorescent probe, NapBu-BPEA, to ensure SIM imaging quality for organelle identification.

Fang H, Geng S, Hao M, Chen Q, Liu M, Liu C, Tian Z, Wang C, Takebe T, Guan JL, Chen Y, Guo Z, He W, Diao J

2020

Generation of human induced pluripotent stem cell-derived liver buds with chemically defined and animal origin-free media

Scientific reports | 21 October

CD-AOF media and supplements ensure the quality and reproducibility of culture systems. This protocol will facilitate the clinical applicability of all iPSC-LBs in the treatment of liver diseases.

Sekine K, Ogawa S, Tsuzuki S, Kobayashi T, Ikeda K, Nakanishi N, Takeuchi K, Kanai E, Otake Y, Okamoto S, Kobayashi T, Takebe T, Taniguchi H

Polygenic architecture informs potential vulnerability to drug-induced liver injury

Nature Medicine | 7 September

Koido et al. revealed genetically defined hepatocyte vulnerability mechanisms to currently unpredictable drug induced liver injury supported by cell-, organoid- and patient-level datasets.

Masaru Koido, Eri Kawakami, Junko Fukumura, Yui Noguchi, Momoko Ohori, Yasunori Nio, Paola Nicoletti, Guruprasad P Aithal, Ann K Daly, Paul B Watkins, Hisashi Anayama, Yvonne Dragan, Tadahiro Shinozawa, Takanori Takebe

Stiffness distribution analysis in indentation depth direction reveals clear mechanical features of cells and organoids by using AFM

Applied Physics Express | 27 August

Kobayashi et al. proposed a method to statistically analyze stiffness distribution in indentation depth direction from multiple force curves measured by AFM.

Kobayashi N, Togo S, Matsuzaki T, Hashiseko K, Kawamura R, Suganuma M, Nakabayashi S, Yoneyama Y, Ouchi R, Takebe T, Yoshikawa H

Generation of multi-cellular human liver organoids from pluripotent stem cells

Methods in Cell Biology | 22 May

Wendy elaborated a human liver organoid culture protocol based on Ouchi et al. Cell Metabolism paper in 2019.

Wendy L. Thompson, Takanori Takebe

Single cell transcriptomics identifies a signaling network coordinating endoderm and mesoderm diversification during foregut organogenesis

Nature Communications | 27 August

Han et al. identified unexpected diversity in mesoderm-derivatives during early foregut organogenesis. This study is highly collaborative work with Aaron Zorn group and Mitsuru Morimoto group at RIKEN.

Lu Han, Praneet Chaturvedi, Keishi Kishimoto, Hiroyuki Koike, Talia Nasr, Kentaro Iwasawa, Kirsten Giesbrecht, Phillip C Witcher, Alexandra Eicher, Lauren Haines, Yarim Lee, John M Shannon, Mitsuru Morimoto, James M Wells, Takanori Takebe, Aaron M Zorn

Orthotopic foetal lung tissue direct injection into lung showed a preventive effect against paraquat-induced acute lung injury in mice

European Journal of Cardio-Thoracic Surgery | 7 April

Okabe et al., in collaboration with thoracic surgeons at Kyoto, extended fetal organ bud transplantation approach towards acute lung injury protection in mouse model.

Ryo Okabe, Toyofumi F Chen-Yoshikawa, Akihiko Yoshizawa, Tsuyoshi Hirashima, Masao Saito, Hiroshi Date, Takanori Takebe

Waiting Time Analysis at University Hospitals Based on Visitor Psychology

International Conference on Human-Computer Interaction | 19 July

Shigeyoshi Iizuka, Shozo Nishii, Eriko Tanimoto, Hiro Nakazawa, Asuka Kodaka, Takanori Takebe

2019

Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids

Cell Metabolism | May 30

Ouchi, R., Togo, S., Kimura, M., Shinozawa, T., Koido, M., Koike, H., Thompson, W., Karns, R. A., Mayhew, C. N., McGrath, P. S., McCauley, H. A., Zhang, R. R., Lewis, K., Hakozaki, S., Ferguson, A., Saiki, N., Yoneyama, Y., Takeuchi, I., Mabuchi, Y., Akazawa, C., Yoshikawa, H. Y., Wells, J. M., Takebe, T.*

Ouchi et al. established a method to generate multicellular organoid models of inflammation and fibrosis that can be used for genetic steatohepatitis modeling.

Featured in Nature Reviews Featured in NIH Director’s Blog

Modelling human hepato-biliary-pancreatic organogenesis from the foregut–midgut boundary

Nature | 25 September

Koike et al. established a multi-organ connection in human stem cell derived organoid model amongst liver, biliary, pancreatic and duodenal tissues.

Koike, H., Iwasawa, K., Ouchi, R., Maezawa, M., Giesbrecht, K., Saiki, N., Ferguson A., Kimura, M., Thompson, W., Wells, J. M., Zorn, A. M. & Takebe, T.

Organoids by design

Science | June 2019

Discussed current and future of designing complex organoids.

Takanori Takebe*, James M. Wells

Creativity for a cure

Nature Medicine | 2019

Invited mini-personal story.

Takanori Takebe

De Novo-Designed Near-Infrared Nanoaggregates for Super-Resolution Monitoring of Lysosomes in Cells, in Whole Organoids and In Vivo

ACS Nano | 4 December

Fang et al. designed a low-toxicity, photostable, near-infrared small molecule fluorescence probe HD-Br for use in the super-resolution imaging of lysosomes.

Fang, H., Yao, S., Chen,Q., Liu, C., Cai, Y., Geng, S., Bai, Y., Tian, Z., Zacharias, A. L., Takebe, T., Chen, Y., Guo, Z., He, W., and Diao, J.

The beta-catenin/YAP signaling axis is a key regulator of melanoma-associated fibroblasts

Signal transduction and targeted therapy | 24 December

T Liu, L Zhou, K Yang, K Iwasawa, AL Kadekaro, T Takebe, T Andl, Y Zhang.

2018

Defining Lineage-Specific Membrane Fluidity Signatures that Regulate Adhesion Kinetics

Stem Cell Reports | 9 October

Takahisa Matsuzaki, Shinya Matsumoto, Toshiharu Kasai, Hiroshi Y. Yoshikawa, Hideki Taniguchi, Takanori Takebe

Optimal Hypoxia Regulates Human iPSC-Derived Liver Bud Differentiation through Intercellular TGFB Signaling

Stem Cell Reports | September 2019

Hiroaki Ayabe, Takahisa Anada, Takuo Kamoya, Tomoya Sato, Masaki Kimura, Emi Yoshizawa, Shunyuu Kikuchi, Yasuharu Ueno, Keisuke Sekine, Gray Camp, Barbara Treutlein, Autumn Ferguson, Osamu Suzuki, Takanori Takebe, Hideki Taniguchi

Digitalized Human Organoid for Wireless Phenotyping

iScience | 31 May

Masaki Kimura, Momoko Azuma, Ran-Ran Zhang, Wendy Thompson, Christopher N. Mayhew, Takanori Takebe

Self-Condensation Culture Enables Vascularization of Tissue Fragments for Efficient Therapeutic Transplantation

Cell Reports | 8 May

Yoshinobu Takahashi, Keisuke Sekine, Tatsuya Kin, Takanori Takebe, Hideki Taniguchi

Selected as cover article

Human iPSC-Derived Posterior Gut Progenitors Are Expandable and Capable of Forming Gut and Liver Organoids

Stem Cell Reports | 13 March

Ran-Ran Zhang, Masaru Koido, Tomomi Tadokoro, Rie Ouchi, Tatsuya Matsuno, Yasuharu Ueno, Keisuke Sekine, Takanori Takebe, Hideki Taniguchi

Tumoroid à la carte: Path for personalization

Hepatology | 19 February

Kyle Lewis, Takanori Takebe

2017

Massive and Reproducible Production of Liver Buds Entirely from Human Pluripotent Stem Cells

Cell Reports | 5 December

Takanori Takebe, Keisuke Sekine, Masaki Kimura, Satoshi Okamoto, Yasuharu Ueno, Hideki Taniguchi

Synergistic Engineering: Organoids Meet Organs-on-a-Chip

Cell Stem Cell | 7 September

Takanori Takebe, Boyang Zhang, Milica Radisic

Advances in Organoid Technology: Hans Clevers, Madeline Lancaster, and Takanori Takebe

Cell Stem Cell | Q&A | 1 June

Hans Clevers, Madeline Lancaster, and Takanori Takebe

Nutritional modulation of mouse and human liver bud growth through a branched-chain amino acid metabolism

Development | 14 March

Hiroyuki Koike, Ran-Ran Zhang, Yasuharu Ueno, Keisuke Sekine, Yun-Wen Zheng, Takanori Takebe, Hideki Taniguchi

Multilineage communication regulates human liver bud development from pluripotency

Nature | 14 June

J. Gray Camp, Keisuke Sekine, Tobias Gerber, Henry Loeffler-Wirth, Hans Binder, Malgorzata Gac, Sabina Kanton, Jorge Kageyama, Georg Damm, Daniel Seehofer, Lenka Belicova, Marc Bickle, Rico Barsacchi, Ryo Okuda, Emi Yoshizawa, Masaki Kimura, Hiroaki Ayabe, Hideki Taniguchi, Takanori Takebe & Barbara Treutlein

Featured in Science
Featured in Cell Systems

2016

Reverse engineering liver buds through self-driven condensation and organization towards medical application

Developmental Biology | 15 December

Tadahiro Shinozawa, Hiroshi Y. Yoshikaw, Takanori Takebe

Growing Mini‐Organs from Stem Cells

Reviews in Cell Biology and Molecular Medicine | November

Hiroyuki Koike, Tamir Rashid, Takanori Takebe

Autotransplantation of Monkey Ear Perichondrium-Derived Progenitor Cells for Cartilage Reconstruction

Cell Transplantation | 1 May

Shintaro Kagimoto, Takanori Takebe, Shinji Kobayashi, Yuichiro Yabuki, Ayaka Hori, Koichi Hirotomi, Taro Mikami, Toshimasa Uemura, Jiro Maegawa, Hideki Taniguchi

Engineering pancreatic tissues from stem cells towards therapy

Regenerative Therapy | March

Yoshinobu Takahashi, Takanori Takebe, Hideki Taniguchi

Generating Mini-Organs in Culture

Current Pathobiology Reports | 11 April

Hiroyuki Koike & Takanori Takebe

2015

Vascularized and Complex Organ Buds from Diverse Tissues via Mesenchymal Cell-Driven Condensation

Cell Stem Cell | 7 May

TakanoriTakebe, Masahiro Enomura, Emi Yoshizawa, Masaki Kimura, Hiroyuki Koike, Yasuharu Ueno, Takahisa Matsuzaki, Takashi Yamazaki, Takafumi Toyohara, Kenji Osafune, Hiromitsu Nakauchi, Hiroshi Y.Yoshikawa, Hideki Taniguchi

Selected as Cover Article
Best of Cell Stem Cell, 2015
News and Views in Cell Stem Cell
Featured in Nature Methods

The boom in mini stomachs, brains, breasts, kidneys and more

Nature | News Feature | 29 July

Cassandra Willyard

2014

Transient vascularization of transplanted human adult–derived progenitors promotes self-organizing cartilage

Journal of Clinical Investigation | 9 September

Takanori Takebe, Shinji Kobayashi, Hiromu Suzuki, Mitsuru Mizuno, Yu-Min Chang, Emi Yoshizawa, Masaki Kimura, Ayaka Hori, Jun Asano, Jiro Maegawa, and Hideki Taniguchi

Novel strategies for liver therapy using stem cells

Stem Cells and Development | 2 September

Rashid T, Takebe T, Nakauchi H.

Brief Report: Reconstruction of Joint Hyaline Cartilage by Autologous Progenitor Cells Derived from Ear Elastic Cartilage

STEM CELLS | 23 August

Mitsuru Mizuno, Shinji Kobayashi, Takanori Takebe, Hiroomi Kan, Yuichiro Yabuki, Takahisa Matsuzaki, Hiroshi Y. Yoshikawa, Seiichiro Nakabayashi, Lee Jeong Ik, Jiro Maegawa, Hideki Taniguchi

Generation of pancreatic beta-cells from pluripotent stem cells

Organ Biology | 10 July

Yoshinobu Takahashi, Takanori Takebe, Hideki Taniguchi.

The CD133 + CD44 + Precancerous Subpopulation of Oval Cells Is a Therapeutic Target for Hepatocellular Carcinoma

Stem Cells and Development | 26 June

Yun-Wen Zheng, Tomonori Tsuchida, Taiki Shimao, Bin Li, Takanori Takebe, Ran-Ran Zhang, Yu Sakurai, Yasuharu Ueno, Keisuke Sekine, Naoto Ishibashi, Makiko Imajima, Takuji Tanaka, and Hideki Taniguchi

Human iPSC‐Derived Miniature Organs: A Tool for Drug Studies

Clinical Pharmacology & Therapeutics | 21 May

T Takebe, H Taniguchi.

Ring1B promotes hepatic stem/progenitor cell expansion through simultaneous suppression of Cdkn1a and Cdkn2a in mice

Hepatology | 4 February

Hiroyuki Koike, Yasuharu Ueno, Takako Naito, Tomoya Shiina, Susumu Nakata, Rie Ouchi, Yuta Obana, Keisuke Sekine, Yun‐Wen Zheng, Takanori Takebe, Kyo‐ichi Isono, Haruhiko Koseki, Hideki Taniguchi

Generation of a vascularized and functional human liver from an iPSC-derived organ bud transplant

Nature Protocols | 23 January

Takanori Takebe, Ran-Ran Zhang, Hiroyuki Koike, Masaki Kimura, Emi Yoshizawa, Masahiro Enomura, Naoto Koike, Keisuke Sekine & Hideki Taniguchi

Engineering of human hepatic tissue with functional vascular networks

Organogenesis | 22 January

Takanori Takebe, Naoto Koike, Keisuke Sekine, Ryoji Fujiwara, Takeru Amiya, Yun-Wen Zheng & Hideki Taniguchi

Vascularized and functional liver devided from human induced pluripotent stem cells by recapitulating organogenesis

Yokohama Medical Journal | January

T. Takebe, H. Taniguchi.

2013

Vascularized and functional human liver from an iPSC-derived organ bud transplant

Nature | 03 July

Takanori Takebe, Keisuke Sekine, Masahiro Enomura, Hiroyuki Koike, Masaki Kimura, Takunori Ogaeri, Ran-Ran Zhang, Yasuharu Ueno, Yun-Wen Zheng, Naoto Koike, Shinsuke Aoyama, Yasuhisa Adachi & Hideki Taniguchi

Selected as Breakthrough of the Year, 2013 in Science

Selected as World top 5 discovery in Discover magazineNews and Views in NatureFeatured in Science, Nature Medicine, Cell Stem Cell, Hepatology, Gastroenterology, Cell Research, etc…

Press in BBC, The Economist, Scientific American, The Guardian, etc…

The generation of pancreatic β-cell spheroids in a simulated microgravity culture system

Biomaterials | July

Hiroyasu Tanaka, Shin Tanaka, Keisuke Sekine, Sayaka Kita, Ai Okamura, Takanori Takebe, Yun-Wen Zheng, Yasuharu Ueno, Junzo Tanaka, Hideki Taniguchi

Creation of vascularized and functional organ from human iPS cell

Organ Biology | 10 July

Takanori Takebe, Hideki Taniguchi.

2012

Establishment of automated culture system for murine induced pluripotent stem cells

BMC Biotechnology | November

Hiroyuki Koike, Koji Kubota, Keisuke Sekine, Takanori Takebe, Rie Ouchi, Yun-Wen Zheng, Yasuharu Ueno, Naoki Tanigawa, Hideki Taniguchi

Generation of Functional Human Vascular Network

Transplantation Proceedings | July

T Takebe, N Koike, K Sekine, M Enomura, Y Chiba, Y Ueno, Y-W Zheng, H Taniguchi

Rudimentary liver grown in vitro

Nature | News Feature | 20 June

David Cyranoski

Self-organization of Human Hepatic Organoid by Recapitulating Organogenesis in Vitro

Transplantation Proceedings | May

T Takebe, K Sekine, Y Suzuki, M Enomura, S Tanaka, Y Ueno, Y-W Zheng, H Taniguchi

2011

Presence of Cartilage Stem/Progenitor Cells in Adult Mice Auricular Perichondrium

PLOS ONE | 19 October

Shinji Kobayashi ,Takanori Takebe ,Yun-Wen Zheng,Mitsuru Mizuno,Yuichiro Yabuki,Jiro Maegawa,Hideki Taniguchi

Reconstruction of human elastic cartilage by a CD44+ CD90+ stem cell in the ear perichondrium

PNAS | 30 August

Shinji Kobayashi, Takanori Takebe, Midori Inui, Sayaka Iwai, Hiroomi Kan, Yun-Wen Zheng, Jiro Maegawa, and Hideki Taniguchi