Human organoids: model systems for human biology and medicine

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30183-5 · Cited by 48,884

A pneumonia outbreak associated with a new coronavirus of probable bat origin

Zhou, P., Yang, X.-L., Wang, X.-G., Hu, B., Zhang, L., Zhang, W., Si, H.-R., Zhu, Y., Li, B., Huang, C.-L., et al. (2020) · Nature · doi:10.1038/s41586-020-2012-7 · Cited by 21,969

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., Schiergens, T. S., Herrler, G., Wu, N.-H., Nitsche, A., et al. (2020) · Cell · doi:10.1016/j.cell.2020.02.052 · Cited by 20,286

Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors

Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007) · Cell · doi:10.1016/j.cell.2007.11.019 · Cited by 20,221

Embryonic Stem Cell Lines Derived from Human Blastocysts

Thomson, J. A., Itskovitz‐Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., & Jones, J. M. (1998) · Science · doi:10.1126/science.282.5391.1145 · Cited by 15,947

Multiplex Genome Engineering Using CRISPR/Cas Systems

Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P. D., Wu, X., Jiang, W., Marraffini, L. A., et al. (2013) · Science · doi:10.1126/science.1231143 · Cited by 15,339

THE GENETICS OF CAENORHABDITIS ELEGANS

Brenner, S. (1974) · Genetics · doi:10.1093/genetics/77.1.71 · Cited by 15,220

Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells

Yu, J., Vodyanik, M. A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J. L., Tian, S., Nie, J., Jonsdottir, G. A., Ruotti, V., Stewart, R., et al. (2007) · Science · doi:10.1126/science.1151526 · Cited by 10,310

RNA-Guided Human Genome Engineering via Cas9

Mali, P., Yang, L., Esvelt, K. M., Aach, J., Guell, M., DiCarlo, J. E., Norville, J. E., & Church, G. M. (2013) · Science · doi:10.1126/science.1232033 · Cited by 9,210

The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2

Gorbalenya, A. E., Baker, S. C., Baric, R. S., de Groot, R. J., Drosten, C., Gulyaeva, A. A., Haagmans, B. L., Lauber, C., Leontovich, A. M., Neuman, B. W., et al. (2020) · Nature Microbiology · doi:10.1038/s41564-020-0695-z · Cited by 8,745

Establishment in culture of pluripotential cells from mouse embryos

Evans, M. J., & Kaufman, M. H. (1981) · Nature · doi:10.1038/292154a0 · Cited by 8,623

Structure, function and antigenicity of the SARS-CoV-2 spike glycoprotein

Walls, A. C., Park, Y.-J., Tortorici, M. A., Wall, A., McGuire, A. T., & Veesler, D. (2020) · doi:10.1101/2020.02.19.956581 · Cited by 8,586

Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche

Sato, T., Vries, R. G., Snippert, H. J., van de Wetering, M., Barker, N., Stange, D. E., van Es, J. H., Abo, A., Kujala, P., Peters, P. J., et al. (2009) · Nature · doi:10.1038/nature07935 · Cited by 7,204

Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus

Li, W., Moore, M. J., Vasilieva, N., Sui, J., Wong, S. K., Berne, M. A., Somasundaran, M., Sullivan, J. L., Luzuriaga, K., Greenough, T. C., et al. (2003) · Nature · doi:10.1038/nature02145 · Cited by 5,923

Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells.

Martin, G. R. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.12.7634 · Cited by 5,756

Identification of stem cells in small intestine and colon by marker gene Lgr5

Barker, N., van Es, J. H., Kuipers, J., Kujala, P., van den Born, M., Cozijnsen, M., Haegebarth, A., Korving, J., Begthel, H., Peters, P. J., et al. (2007) · Nature · doi:10.1038/nature06196 · Cited by 5,687

Cerebral organoids model human brain development and microcephaly

Lancaster, M. A., Renner, M., Martin, C.-A., Wenzel, D., Bicknell, L. S., Hurles, M. E., Homfray, T., Penninger, J. M., Jackson, A. P., & Knoblich, J. A. (2013) · Nature · doi:10.1038/nature12517 · Cited by 5,372

Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2

Yan, R., Zhang, Y., Li, Y., Xia, L., Guo, Y., & Zhou, Q. (2020) · Science · doi:10.1126/science.abb2762 · Cited by 5,036

The embryonic cell lineage of the nematode Caenorhabditis elegans

Sulston, J. E., Schierenberg, E., White, J. G., & Thomson, J. N. (1983) · Developmental Biology · doi:10.1016/0012-1606(83)90201-4 · Cited by 4,199

Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium

Sato, T., Stange, D. E., Ferrante, M., Vries, R. G. J., van Es, J. H., van den Brink, S., van Houdt, W. J., Pronk, A., van Gorp, J., Siersema, P. D., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.07.050 · Cited by 3,753

Structural basis of receptor recognition by SARS-CoV-2

Shang, J., Ye, G., Shi, K., Wan, Y., Luo, C., Aihara, H., Geng, Q., Auerbach, A., & Li, F. (2020) · Nature · doi:10.1038/s41586-020-2179-y · Cited by 3,661

One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering

Wang, H., Yang, H., Shivalila, C. S., Dawlaty, M. M., Cheng, A. W., Zhang, F., & Jaenisch, R. (2013) · Cell · doi:10.1016/j.cell.2013.04.025 · Cited by 3,495

The ground state of embryonic stem cell self-renewal

Ying, Q.-L., Wray, J., Nichols, J., Batlle-Morera, L., Doble, B., Woodgett, J., Cohen, P., & Smith, A. (2008) · Nature · doi:10.1038/nature06968 · Cited by 3,442

Modeling Development and Disease with Organoids

Clevers, H. (2016) · Cell · doi:10.1016/j.cell.2016.05.082 · Cited by 3,196

Organogenesis in a dish: Modeling development and disease using organoid technologies

Lancaster, M. A., & Knoblich, J. A. (2014) · Science · doi:10.1126/science.1247125 · Cited by 2,931

Zika Virus Associated with Microcephaly

Mlakar, J., Korva, M., Tul, N., Popović, M., Poljšak-Prijatelj, M., Mraz, J., Kolenc, M., Resman Rus, K., Vesnaver Vipotnik, T., Fabjan Vodušek, V., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1600651 · Cited by 2,884

SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes

HCA Lung Biological Network, Sungnak, W., Huang, N., Bécavin, C., Berg, M., Queen, R., Litvinukova, M., Talavera-López, C., Maatz, H., Reichart, D., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0868-6 · Cited by 2,501

Prospective Derivation of a Living Organoid Biobank of Colorectal Cancer Patients

van de Wetering, M., Francies, H. E., Francis, J. M., Bounova, G., Iorio, F., Pronk, A., van Houdt, W., van Gorp, J., Taylor-Weiner, A., Kester, L., et al. (2015) · Cell · doi:10.1016/j.cell.2015.03.053 · Cited by 2,408

Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells

Thomas, K. R., & Capecchi, M. R. (1987) · Cell · doi:10.1016/0092-8674(87)90646-5 · Cited by 2,355

New cell lines from mouse epiblast share defining features with human embryonic stem cells

Tesar, P. J., Chenoweth, J. G., Brook, F. A., Davies, T. J., Evans, E. P., Mack, D. L., Gardner, R. L., & McKay, R. D. G. (2007) · Nature · doi:10.1038/nature05972 · Cited by 2,187

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

Takebe, T., Sekine, K., Enomura, M., Koike, H., Kimura, M., Ogaeri, T., Zhang, R.-R., Ueno, Y., Zheng, Y.-W., Koike, N., et al. (2013) · Nature · doi:10.1038/nature12271 · Cited by 2,170

Organoid models of human and mouse ductal pancreatic cancer

Boj, S. F., Hwang, C.-I., Baker, L. A., Chio, I. I. C., Engle, D. D., Corbo, V., Jager, M., Ponz-Sarvise, M., Tiriac, H., Spector, M. S., et al. (2015) · Cell · doi:10.1016/j.cell.2014.12.021 · Cited by 2,150

Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2

Monteil, V., Kwon, H., Prado, P., Hagelkrüys, A., Wimmer, R. A., Stahl, M., Leopoldi, A., Garreta, E., Hurtado del Pozo, C., Prosper, F., et al. (2020) · Cell · doi:10.1016/j.cell.2020.04.004 · Cited by 2,122

A TALE nuclease architecture for efficient genome editing

Miller, J. C., Tan, S., Qiao, G., Barlow, K. A., Wang, J., Xia, D. F., Meng, X., Paschon, D. E., Leung, E., Hinkley, S. J., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1755 · Cited by 2,098

Patient-derived organoids model treatment response of metastatic gastrointestinal cancers

Vlachogiannis, G., Hedayat, S., Vatsiou, A., Jamin, Y., Fernández-Mateos, J., Khan, K., Lampis, A., Eason, K., Huntingford, I., Burke, R., et al. (2018) · Science · doi:10.1126/science.aao2774 · Cited by 2,096

Derivation of pluripotent epiblast stem cells from mammalian embryos

Brons, I. G. M., Smithers, L. E., Trotter, M. W. B., Rugg‐Gunn, P. J., Sun, B., Lopes, S. M. C. D. S., Howlett, S., Clarkson, A., Ährlund‐Richter, L., Pedersen, R. A., et al. (2007) · Nature · doi:10.1038/nature05950 · Cited by 2,007

Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells

Williams, R. L., Hilton, D. J., Pease, S., Willson, T. A., Stewart, C. L., Gearing, D. P., Wagner, E. F., Metcalf, D., Nicola, N. A., & Gough, N. M. (1988) · Nature · doi:10.1038/336684a0 · Cited by 1,997

A living biobank of breast cancer organoids captures disease heterogeneity

Sachs, N., de Ligt, J., Kopper, O., Gogola, E., Bounova, G., Weeber, F., Balgobind, A. V., Wind, K., Gracanin, A., Begthel, H., et al. (2018) · Cell · doi:10.1016/j.cell.2017.11.010 · Cited by 1,973

Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro

Spence, J. R., Mayhew, C. N., Rankin, S. A., Kuhar, M. F., Vallance, J. E., Tolle, K. A., Hoskins, E. E., Kalinichenko, V. V., Wells, S. I., Zorn, A. M., et al. (2010) · Nature · doi:10.1038/nature09691 · Cited by 1,911

Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease

Cho, S. W., Kim, S., Kim, J. M., & Kim, J.-S. (2013) · Nature Biotechnology · doi:10.1038/nbt.2507 · Cited by 1,863

Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides

Smith, A. G., Heath, J. K., Donaldson, D. D., Wong, G. G., Moreau, J., Stahl, M., & Rogers, D. D. (1988) · Nature · doi:10.1038/336688a0 · Cited by 1,855

RNA-guided genetic silencing systems in bacteria and archaea

Wiedenheft, B., Sternberg, S. H., & Doudna, J. A. (2012) · Nature · doi:10.1038/nature10886 · Cited by 1,851

Organoids in cancer research

Drost, J., & Clevers, H. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0007-6 · Cited by 1,790

Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis

Takasato, M., Er, P. X., Chiu, H. S., Maier, B., Baillie, G. J., Ferguson, C., Parton, R. G., Wolvetang, E. J., Roost, M. S., Chuva de Sousa Lopes, S. M., et al. (2015) · Nature · doi:10.1038/nature15695 · Cited by 1,627

Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver

Huch, M., Gehart, H., van Boxtel, R., Hamer, K., Blokzijl, F., Verstegen, M. M. A., Ellis, E., van Wenum, M., Fuchs, S. A., de Ligt, J., et al. (2015) · Cell · doi:10.1016/j.cell.2014.11.050 · Cited by 1,619

One-step generation of mice carrying reporter and conditional alleles by CRISPR/Cas-mediated genome engineering

Yang, H., Wang, H., Shivalila, C. S., Cheng, A. W., Shi, L., & Jaenisch, R. (2013) · Cell · doi:10.1016/j.cell.2013.08.022 · Cited by 1,596

Basal cells as stem cells of the mouse trachea and human airway epithelium

Rock, J. R., Onaitis, M. W., Rawlins, E. L., Lu, Y., Clark, C. P., Xue, Y., Randell, S. H., & Hogan, B. L. M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906850106 · Cited by 1,591

SARS-CoV-2 productively infects human gut enterocytes

Lamers, M. M., Beumer, J., van der Vaart, J., Knoops, K., Puschhof, J., Breugem, T. I., Ravelli, R. B. G., Paul van Schayck, J., Mykytyn, A. Z., Duimel, H. Q., et al. (2020) · Science · doi:10.1126/science.abc1669 · Cited by 1,573

Organoid Cultures Derived from Patients with Advanced Prostate Cancer

Gao, D., Vela, I., Sboner, A., Iaquinta, P. J., Karthaus, W. R., Gopalan, A., Dowling, C., Wanjala, J. N., Undvall, E. A., Arora, V. K., et al. (2014) · Cell · doi:10.1016/j.cell.2014.08.016 · Cited by 1,559

Organoid modeling of the tumor immune microenvironment

Neal, J. T., Li, X., Zhu, J., Giangarra, V., Grzeskowiak, C. L., Ju, J., Liu, I. H., Chiou, S.-H., Salahudeen, A. A., Smith, A. R., et al. (2018) · Cell · doi:10.1016/j.cell.2018.11.021 · Cited by 1,556

In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration

Huch, M., Dorrell, C., Boj, S. F., van Es, J. H., Li, V. S. W., van de Wetering, M., Sato, T., Hamer, K., Sasaki, N., Finegold, M. J., et al. (2013) · Nature · doi:10.1038/nature11826 · Cited by 1,555

Lgr5+ve Stem Cells Drive Self-Renewal in the Stomach and Build Long-Lived Gastric Units In Vitro

Barker, N., Huch, M., Kujala, P., van de Wetering, M., Snippert, H. J., van Es, J. H., Sato, T., Stange, D. E., Begthel, H., van den Born, M., et al. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2009.11.013 · Cited by 1,547

Organoids as an in vitro model of human development and disease

Fatehullah, A., Tan, S. H., & Barker, N. (2016) · Nature Cell Biology · doi:10.1038/ncb3312 · Cited by 1,508

Human primary liver cancer–derived organoid cultures for disease modeling and drug screening

Broutier, L., Mastrogiovanni, G., Verstegen, M. M., Francies, H. E., Gavarró, L. M., Bradshaw, C. R., Allen, G. E., Arnes-Benito, R., Sidorova, O., Gaspersz, M. P., et al. (2017) · Nature Medicine · doi:10.1038/nm.4438 · Cited by 1,471

The next generation of CRISPR–Cas technologies and applications

Pickar-Oliver, A., & Gersbach, C. A. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0131-5 · Cited by 1,459

Designer matrices for intestinal stem cell and organoid culture

Gjorevski, N., Sachs, N., Manfrin, A., Giger, S., Bragina, M. E., Ordóñez-Morán, P., Clevers, H., & Lutolf, M. P. (2016) · Nature · doi:10.1038/nature20168 · Cited by 1,426

Functional Repair of CFTR by CRISPR/Cas9 in Intestinal Stem Cell Organoids of Cystic Fibrosis Patients

Schwank, G., Koo, B.-K., Sasselli, V., Dekkers, J. F., Heo, I., Demircan, T., Sasaki, N., Boymans, S., Cuppen, E., van der Ent, C. K., et al. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2013.11.002 · Cited by 1,424

Assembly of functionally integrated human forebrain spheroids

Birey, F., Andersen, J., Makinson, C. D., Islam, S., Wei, W., Huber, N., Fan, H. C., Metzler, K. R. C., Panagiotakos, G., Thom, N., et al. (2017) · Nature · doi:10.1038/nature22330 · Cited by 1,365

Development and Evolution of the Human Neocortex

Lui, J. H., Hansen, D. V., & Kriegstein, A. R. (2011) · Cell · doi:10.1016/j.cell.2011.06.030 · Cited by 1,342

The Brazilian Zika virus strain causes birth defects in experimental models

Cugola, F. R., Fernandes, I. R., Russo, F. B., Freitas, B. C., Dias, J. L. M., Guimarães, K. P., Benazzato, C., Almeida, N., Pignatari, G. C., Romero, S., et al. (2016) · Nature · doi:10.1038/nature18296 · Cited by 1,326

Replication of human noroviruses in stem cell–derived human enteroids

Ettayebi, K., Crawford, S. E., Murakami, K., Broughman, J. R., Karandikar, U., Tenge, V. R., Neill, F. H., Blutt, S. E., Zeng, X.-L., Qu, L., et al. (2016) · Science · doi:10.1126/science.aaf5211 · Cited by 1,305

SARS-CoV-2 Entry Genes Are Most Highly Expressed in Nasal Goblet and Ciliated Cells within Human Airways.Preprint

Sungnak, W., Huang, N., Bécavin, C., & Berg, M. (2020) · PubMed · Cited by 1,196

Zika virus impairs growth in human neurospheres and brain organoids

Garcez, P. P., Loiola, E. C., Madeiro da Costa, R., Higa, L. M., Trindade, P., Delvecchio, R., Nascimento, J. M., Brindeiro, R., Tanuri, A., & Rehen, S. K. (2016) · Science · doi:10.1126/science.aaf6116 · Cited by 1,184

Progress and potential in organoid research

Rossi, G., Manfrin, A., & Lutolf, M. P. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0051-9 · Cited by 1,182

Induction of Pluripotent Stem Cells From Adult Human Fibroblasts by Defined Factors

Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2008) · Obstetrical & Gynecological Survey · doi:10.1097/01.ogx.0000305204.97355.0d · Cited by 1,174

Detection and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: a case study

Calvet, G. A., Aguiar, R. S., Melo, A., Sampaio, S. A., de Filippis, I., Fabri, A. D. A., de Araújo, E. S. M., de Sequeira, P. C., de Mendonça, M. C. L., de Oliveira, L., et al. (2016) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(16)00095-5 · Cited by 1,164

A Patient-Derived Glioblastoma Organoid Model and Biobank Recapitulates Inter- and Intra-tumoral Heterogeneity

Jacob, F., Salinas, R. D., Zhang, D. Y., Nguyen, P. T. T., Schnoll, J. G., Wong, S. Z. H., Thokala, R., Sheikh, S., Saxena, D., Prokop, S., et al. (2020) · Cell · doi:10.1016/j.cell.2019.11.036 · Cited by 1,149

A developmental and genetic classification for malformations of cortical development: update 2012

Barkovich, A. J., Guerrini, R., Kuzniecky, R., Jackson, G. D., & Dobyns, W. B. (2012) · Brain · doi:10.1093/brain/aws019 · Cited by 1,146

Modeling colorectal cancer using CRISPR-Cas9–mediated engineering of human intestinal organoids

Matano, M., Date, S., Shimokawa, M., Takano, A., Fujii, M., Ohta, Y., Watanabe, T., Kanai, T., & Sato, T. (2015) · Nature Medicine · doi:10.1038/nm.3802 · Cited by 1,135

Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids

Dijkstra, K. K., Cattaneo, C. M., Weeber, F., Chalabi, M., van de Haar, J., Fanchi, L. F., Slagter, M., van der Velden, D. L., Kaing, S., Kelderman, S., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.009 · Cited by 1,135

Long‐term expanding human airway organoids for disease modeling

Sachs, N., Papaspyropoulos, A., Zomer‐van Ommen, D. D., Heo, I., Böttinger, L., Klay, D., Weeber, F., Huelsz‐Prince, G., Iakobachvili, N., Amatngalim, G. D., et al. (2019) · The EMBO Journal · doi:10.15252/embj.2018100300 · Cited by 1,082

Sequential cancer mutations in cultured human intestinal stem cells

Drost, J., van Jaarsveld, R. H., Ponsioen, B., Zimberlin, C., van Boxtel, R., Buijs, A., Sachs, N., Overmeer, R. M., Offerhaus, G. J., Begthel, H., et al. (2015) · Nature · doi:10.1038/nature14415 · Cited by 1,067

Derivation of novel human ground state naive pluripotent stem cells

Gafni, O., Weinberger, L., Mansour, A. A., Manor, Y. S., Chomsky, E., Ben‐Yosef, D., Kalma, Y., Viukov, S. V., Maza, I., Zviran, A., et al. (2013) · Nature · doi:10.1038/nature12745 · Cited by 1,058

A functional CFTR assay using primary cystic fibrosis intestinal organoids

Dekkers, J. F., Wiegerinck, C. L., de Jonge, H. R., Bronsveld, I., Janssens, H. M., de Winter-de Groot, K. M., Brandsma, A. M., de Jong, N. W. M., Bijvelds, M. J. C., Scholte, B. J., et al. (2013) · Nature Medicine · doi:10.1038/nm.3201 · Cited by 999

Modelling human development and disease in pluripotent stem-cell-derived gastric organoids

McCracken, K. W., Catá, E. M., Crawford, C. M., Sinagoga, K. L., Schumacher, M., Rockich, B. E., Tsai, Y.-H., Mayhew, C. N., Spence, J. R., Zavros, Y., et al. (2014) · Nature · doi:10.1038/nature13863 · Cited by 980

Resetting Transcription Factor Control Circuitry toward Ground-State Pluripotency in Human

Takashima, Y., Guo, G., Loos, R., Nichols, J., Ficz, G., Krueger, F., Oxley, D., Santos, F., Clarke, J., Mansfield, W. M., et al. (2014) · Cell · doi:10.1016/j.cell.2014.08.029 · Cited by 959

Systematic Identification of Culture Conditions for Induction and Maintenance of Naive Human Pluripotency

Theunissen, T. W., Powell, B. E., Wang, H., Mitalipova, M., Faddah, D. A., Reddy, J., Fan, Z. P., Maetzel, D., Ganz, K., Shi, L., et al. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.07.002 · Cited by 888

Tumor Evolution and Drug Response in Patient-Derived Organoid Models of Bladder Cancer

Lee, S. H., Hu, W., Matulay, J. T., Silva, M. V., Owczarek, T. B., Kim, K., Chua, C. W., Barlow, L. J., Kandoth, C., Williams, A. B., et al. (2018) · Cell · doi:10.1016/j.cell.2018.03.017 · Cited by 873

A Colorectal Tumor Organoid Library Demonstrates Progressive Loss of Niche Factor Requirements during Tumorigenesis

Fujii, M., Shimokawa, M., Date, S., Takano, A., Matano, M., Nanki, K., Ohta, Y., Toshimitsu, K., Nakazato, Y., Kawasaki, K., et al. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.04.003 · Cited by 852

In vitro generation of human pluripotent stem cell derived lung organoids

Dye, B. R., Hill, D. R., Ferguson, M. A. H., Tsai, Y.-H., Nagy, M. S., Dyal, R., Wells, J. M., Mayhew, C. N., Nattiv, R., Klein, O. D., et al. (2015) · eLife · doi:10.7554/elife.05098 · Cited by 846

Disease modeling in stem cell-derived 3D organoid systems

Dutta, D., Heo, I., & Clevers, H. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.02.007 · Cited by 838

Long-Term Expansion of Functional Mouse and Human Hepatocytes as 3D Organoids

Hu, H., Gehart, H., Artegiani, B., LÖpez-Iglesias, C., Dekkers, F., Basak, O., van Es, J., Chuva de Sousa Lopes, S. M., Begthel, H., Korving, J., et al. (2018) · Cell · doi:10.1016/j.cell.2018.11.013 · Cited by 837

Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors

Zhang, Y. S., Aleman, J., Shin, S. R., Kilic, T., Kim, D., Mousavi Shaegh, S. A., Massa, S., Riahi, R., Chae, S., Hu, N., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1612906114 · Cited by 833

Enhancing Gene Targeting with Designed Zinc Finger Nucleases

Bibikova, M. V., Beumer, K. J., Trautman, J. K., & Carroll, D. (2003) · Science · doi:10.1126/science.1079512 · Cited by 824

In Vitro Expansion of Human Gastric Epithelial Stem Cells and Their Responses to Bacterial Infection

Bartfeld, S., Bayram, T., van de Wetering, M., Huch, M., Begthel, H., Kujala, P., Vries, R., Peters, P. J., & Clevers, H. (2015) · Gastroenterology · doi:10.1053/j.gastro.2014.09.042 · Cited by 820

Patient-derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients

Ooft, S. N., Weeber, F., Dijkstra, K. K., McLean, C. M., Kaing, S., van Werkhoven, E., Schipper, L., Hoes, L., Vis, D. J., van de Haar, J., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aay2574 · Cited by 813

Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening

Kim, M., Mun, H., Sung, C. O., Cho, E. J., Jeon, H.-J., Chun, S.-M., Jung, D. J., Shin, T. H., Jeong, G. S., Kim, D. K., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11867-6 · Cited by 812

Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium

Turco, M. Y., Gardner, L., Hughes, J., Cindrová‐Davies, T., Gómez‐Ruíz, M., Farrell, L. E., Hollinshead, M. S., Marsh, S. G. E., Brosens, J. J., Critchley, H., et al. (2017) · Nature Cell Biology · doi:10.1038/ncb3516 · Cited by 809

Human blood vessel organoids as a model of diabetic vasculopathy

Wimmer, R. A., Leopoldi, A., Aichinger, M., Wick, N., Hantusch, B., Novatchkova, M., Taubenschmid, J., Hämmerle, M., Esk, C., Bagley, J. A., et al. (2019) · Nature · doi:10.1038/s41586-018-0858-8 · Cited by 803

Fused cerebral organoids model interactions between brain regions

Bagley, J. A., Reumann, D., Bian, S., Lévi-Strauss, J., & Knoblich, J. A. (2017) · Nature Methods · doi:10.1038/nmeth.4304 · Cited by 790

Guided self-organization and cortical plate formation in human brain organoids

Lancaster, M. A., Corsini, N. S., Wolfinger, S., Gustafson, E. H., Phillips, A. W., Burkard, T. R., Otani, T., Livesey, F. J., & Knoblich, J. A. (2017) · Nature Biotechnology · doi:10.1038/nbt.3906 · Cited by 783

Large-scale mutagenesis in the zebrafish: in search of genes controlling development in a vertebrate

Mullins, M. C., Hammerschmidt, M., Haffter, P., & Nüsslein‐Volhard, C. (1994) · Current Biology · doi:10.1016/s0960-9822(00)00048-8 · Cited by 764

Patient-Derived Organoids Predict Chemoradiation Responses of Locally Advanced Rectal Cancer

Yao, Y., Xu, X., Yang, L., Zhu, J., Wan, J., Shen, L., Xia, F., Fu, G., Deng, Y., Pan, M., et al. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2019.10.010 · Cited by 755

Chimeric nucleases stimulate gene targeting in human cells

Porteus, M. H., & Baltimore, D. (2003) · Science · doi:10.1126/science.1078395 · Cited by 741

Identification of Multipotent Luminal Progenitor Cells in Human Prostate Organoid Cultures

Karthaus, W. R., Iaquinta, P. J., Drost, J., Gracanin, A., van Boxtel, R., Wongvipat, J., Dowling, C., Gao, D., Begthel, H., Sachs, N., et al. (2014) · Cell · doi:10.1016/j.cell.2014.08.017 · Cited by 739

Zika Virus Depletes Neural Progenitors in Human Cerebral Organoids through Activation of the Innate Immune Receptor TLR3

Dang, J., Tiwari, S. K., Lichinchi, G., Qin, Y., Patil, V. S., Eroshkin, A. M., & Rana, T. M. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.04.014 · Cited by 731

Unlimited in vitro expansion of adult bi‐potent pancreas progenitors through the Lgr5/R‐spondin axis

Huch, M., Bonfanti, P., Boj, S. F., Sato, T., Loomans, C. J. M., van de Wetering, M., Sojoodi, M., Li, V. S. W., Schuijers, J., Gracanin, A., et al. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.204 · Cited by 726

A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening

Yan, H. H. N., Siu, H. C., Law, S., Ho, S. L., Yue, S. S. K., Tsui, W. Y., Chan, D., Chan, A. S., Ma, S., Lam, K. O., et al. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.09.016 · Cited by 724

WormBase: a multi-species resource for nematode biology and genomics

Harris, T. W. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkh066 · Cited by 717

Fusion of Regionally Specified hPSC-Derived Organoids Models Human Brain Development and Interneuron Migration

Xiang, Y., Tanaka, Y., Patterson, B., Kang, Y., Govindaiah, G., Roselaar, N., Çakır, B., Kim, K.-Y., Lombroso, A., Hwang, S., et al. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.07.007 · Cited by 711

Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen

Xu, M., Lee, E. M., Wen, Z., Cheng, Y., Huang, W.-K., Qian, X., Julia, T. C. W., Kouznetsova, J., Ogden, S. C., Hammack, C., et al. (2016) · Nature Medicine · doi:10.1038/nm.4184 · Cited by 651

Human Pancreatic Tumor Organoids Reveal Loss of Stem Cell Niche Factor Dependence during Disease Progression

Seino, T., Kawasaki, S., Shimokawa, M., Tamagawa, H., Toshimitsu, K., Fujii, M., Ohta, Y., Matano, M., Nanki, K., Kawasaki, K., et al. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2017.12.009 · Cited by 631

The intestinal stem cell

Barker, N., van de Wetering, M., & Clevers, H. (2008) · Genes & Development · doi:10.1101/gad.1674008 · Cited by 629

Organoids: A historical perspective of thinking in three dimensions

Simian, M., & Bissell, M. J. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201610056 · Cited by 620

Pluripotent stem cells in disease modelling and drug discovery

Avior, Y., Sagi, I., & Benvenisty, N. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2015.27 · Cited by 592

Metabolic costs and evolutionary implications of human brain development

Kuzawa, C. W., Chugani, H. T., Grossman, L. I., Lipovich, L., Muzik, O., Hof, P. R., Wildman, D. E., Sherwood, C. C., Leonard, W. R., & Lange, N. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1323099111 · Cited by 585

Modeling mouse and human development using organoid cultures

Huch, M., & Koo, B. (2015) · Development · doi:10.1242/dev.118570 · Cited by 578

A rectal cancer organoid platform to study individual responses to chemoradiation

Ganesh, K., Wu, C., O’Rourke, K. P., Szeglin, B. C., Zheng, Y., Sauvé, C.-E. G., Adileh, M., Wasserman, I., Marco, M. R., Kim, A. S., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0584-2 · Cited by 569

Human Intestinal Organoids Maintain Self-Renewal Capacity and Cellular Diversity in Niche-Inspired Culture Condition

Fujii, M., Matano, M., Toshimitsu, K., Takano, A., Mikami, Y., Nishikori, S., Sugimoto, S., & Sato, T. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.11.016 · Cited by 558

Advances in Pluripotent Stem Cells: History, Mechanisms, Technologies, and Applications

Liu, G., David, B. T., Trawczynski, M., & Fessler, R. G. (2019) · Stem Cell Reviews and Reports · doi:10.1007/s12015-019-09935-x · Cited by 557

Generating genetically modified mice using CRISPR/Cas-mediated genome engineering

Yang, H., Wang, H., & Jaenisch, R. (2014) · Nature Protocols · doi:10.1038/nprot.2014.134 · Cited by 554

Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis

Dekkers, J. F., Berkers, G., Kruisselbrink, E., Vonk, A., de Jonge, H. R., Janssens, H. M., Bronsveld, I., van de Graaf, E. A., Nieuwenhuis, E. E. S., Houwen, R. H. J., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad8278 · Cited by 548

Differentiated Troy+ Chief Cells Act as Reserve Stem Cells to Generate All Lineages of the Stomach Epithelium

Stange, D. E., Koo, B., Huch, M., Sibbel, G., Başak, O., Lyubimova, A., Kujala, P., Bartfeld, S., Köster, J., Geahlen, J. H., et al. (2013) · Cell · doi:10.1016/j.cell.2013.09.008 · Cited by 523

Patient-derived organoids from endometrial disease capture clinical heterogeneity and are amenable to drug screening

Boretto, M., Maenhoudt, N., Luo, X., Hennes, A., Boeckx, B., Bui, B. N., Heremans, R., Perneel, L., Kobayashi, H., Zundert, I. V., et al. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0360-z · Cited by 517

Exploring host–microbiota interactions in animal models and humansPreprint

Kostic, A. D., Howitt, M. R., & Garrett, W. S. (2013) · Genes & Development · doi:10.1101/gad.212522.112 · Cited by 516

Induced Pluripotent Stem Cell Lines Derived From Human Somatic Cells

Yu, J., Vodyanik, M. A., Smuga-Otto, K., Antosiewicz‐Bourget, J., Frane, J. L., Tian, S., Nie, J., Jónsdóttir, G. A., Ruotti, V., Stewart, R. M., et al. (2008) · Obstetrical & Gynecological Survey · doi:10.1097/01.ogx.0000305193.72586.39 · Cited by 514

Extracellular matrix hydrogel derived from decellularized tissues enables endodermal organoid culture

Giobbe, G. G., Crowley, C., Luni, C., Campinoti, S., Khedr, M., Kretzschmar, K., De Santis, M. M., Zambaiti, E., Michielin, F., Meran, L., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13605-4 · Cited by 500

Organoids: Modeling Development and the Stem Cell Niche in a Dish

Kretzschmar, K., & Clevers, H. C. (2016) · Developmental Cell · doi:10.1016/j.devcel.2016.08.014 · Cited by 496

Preserved genetic diversity in organoids cultured from biopsies of human colorectal cancer metastases

Weeber, F., van de Wetering, M., Hoogstraat, M., Dijkstra, K. K., Krijgsman, O., Kuilman, T., Gadellaa-van Hooijdonk, C. G. M., van der Velden, D. L., Peeper, D. S., Cuppen, E. P. J. G., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1516689112 · Cited by 482

Pancreatic cancer organoids recapitulate disease and allow personalized drug screening

Driehuis, E., van Hoeck, A., Moore, K., Kolders, S., Francies, H. E., Gülersönmez, M. C., Stigter, E. C. A., Burgering, B. M. T., Geurts, V., Gracanin, A., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1911273116 · Cited by 471

Influenza Virus Neuraminidase Structure and Functions

McAuley, J., Gilbertson, B. P., Trifkovic, S., Brown, L. E., & McKimm‐Breschkin, J. L. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.00039 · Cited by 471

Derivation of naïve human embryonic stem cells

Ware, C. B., Nelson, A. M., Mecham, B. H., Hesson, J., Zhou, W., Jonlin, E. C., Jiménez‐Caliani, A. J., Deng, X., Cavanaugh, C., Cook, S. M., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1319738111 · Cited by 470

The Notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids

Kessler, M., Hoffmann, K., Brinkmann, V., Thieck, O., Jackisch, S., Toelle, B., Berger, H., Mollenkopf, H., Mangler, M., Sehouli, J., et al. (2015) · Nature Communications · doi:10.1038/ncomms9989 · Cited by 468

Development of organoids from mouse and human endometrium showing endometrial epithelium physiology and long-term expandability

Boretto, M., Cox, B., Noben, M., Hendriks, N., Fassbender, A., Roose, H., Amant, F., Timmerman, D., Tomassetti, C., Vanhie, A., et al. (2017) · Development · doi:10.1242/dev.148478 · Cited by 459

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

Takebe, T., Enomura, M., Yoshizawa, E., Kimura, M., Koike, H., Ueno, Y., Matsuzaki, T., Yamazaki, T., Toyohara, T., Osafune, K., et al. (2015) · Cell stem cell · doi:10.1016/j.stem.2015.03.004 · Cited by 454

A primary human macrophage-enteroid co-culture model to investigate mucosal gut physiology and host-pathogen interactions

Noel, G., Baetz, N. W., Staab, J. F., Donowitz, M., Kovbasnjuk, O., Pasetti, M. F., & Zachos, N. C. (2017) · Scientific Reports · doi:10.1038/srep45270 · Cited by 420

Zika virus and microcephaly: why is this situation a PHEIC?

Heymann, D. L., Hodgson, A., Sall, A. A., Freedman, D. O., Staples, J. E., Althabe, F., Baruah, K., Mahmud, G., Kandun, N., Vasconcelos, P. F. C., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00320-2 · Cited by 415

Recapitulation of SARS-CoV-2 infection and cholangiocyte damage with human liver ductal organoids

Zhao, B. T., Ni, C., Gao, R., Wang, Y., Li, Y., Wei, J., Lv, T., Liang, J., Zhang, Q., Xu, W., et al. (2020) · Protein & Cell · doi:10.1007/s13238-020-00718-6 · Cited by 408

Induction of a Human Pluripotent State with Distinct Regulatory Circuitry that Resembles Preimplantation Epiblast

Chan, Y.-S., Göke, J., Ng, J.-H., Lu, X., Gonzales, K. A. U., Tan, C.-P., Tng, W. J., Hong, Z.-Z., Lim, Y. S., & Ng, H. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.11.015 · Cited by 392

Disease modelling in human organoids

Lancaster, M. A., & Huch, M. (2019) · Disease Models & Mechanisms · doi:10.1242/dmm.039347 · Cited by 390

Modelling Cryptosporidium infection in human small intestinal and lung organoids

Heo, I., Dutta, D., Schaefer, D. A., Iakobachvili, N., Artegiani, B., Sachs, N., Boonekamp, K. E., Bowden, G. D., Hendrickx, A. P. A., Willems, R. J. L., et al. (2018) · Nature Microbiology · doi:10.1038/s41564-018-0177-8 · Cited by 386

Stem Cell Models of Human Brain Development

Kelava, I., & Lancaster, M. A. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.05.022 · Cited by 385

Human Intestinal Enteroids: a New Model To Study Human Rotavirus Infection, Host Restriction, and Pathophysiology

Saxena, K., Blutt, S. E., Ettayebi, K., Zeng, X.-L., Broughman, J. R., Crawford, S. E., Karandikar, U. C., Sastri, N. P., Conner, M. E., Opekun, A. R., et al. (2016) · Journal of Virology · doi:10.1128/jvi.01930-15 · Cited by 375

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

Takebe, T., Zhang, R., Koike, H., Kimura, M., Yoshizawa, E., Enomura, M., Koike, N., Sekine, K., & Taniguchi, H. (2014) · Nature Protocols · doi:10.1038/nprot.2014.020 · Cited by 366

Anatomically and Functionally Distinct Lung Mesenchymal Populations Marked by Lgr5 and Lgr6

Lee, J., Tammela, T., Hofree, M., Choi, J., Marjanovic, N. D., Han, S., Canner, D. A., Wu, K., Paschini, M., Bhang, D. H., et al. (2017) · Cell · doi:10.1016/j.cell.2017.07.028 · Cited by 363

Naive Pluripotent Stem Cells Derived Directly from Isolated Cells of the Human Inner Cell Mass

Guo, G., von Meyenn, F., Santos, F., Chen, Y., Reik, W., Bertone, P., Smith, A. G., & Nichols, J. (2016) · Stem Cell Reports · doi:10.1016/j.stemcr.2016.02.005 · Cited by 362

Single luminal epithelial progenitors can generate prostate organoids in culture

Chua, C. W., Shibata, M., Lei, M., Toivanen, R., Barlow, L. J., Bergren, S. K., Badani, K. K., McKiernan, J. M., Benson, M. C., Hibshoosh, H. H., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb3047 · Cited by 361

Organoids in immunological research

Bar-Ephraim, Y. E., Kretzschmar, K., & Clevers, H. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0248-y · Cited by 361

Liver organoids: from basic research to therapeutic applications

Prior, N., Inacio, P., & Huch, M. (2019) · Gut · doi:10.1136/gutjnl-2019-319256 · Cited by 356

3D model for CAR‐mediated cytotoxicity using patient‐derived colorectal cancer organoids

Schnalzger, T. E., de Groot, M. H., Zhang, C., Mosa, M. H., Michels, B. E., Röder, J., Darvishi, T., Wels, W. S., & Farin, H. F. (2019) · The EMBO Journal · doi:10.15252/embj.2018100928 · Cited by 354

Towards a human-on-chip: Culturing multiple cell types on a chip with compartmentalized microenvironments

Zhang, C., Zhao, Z., Abdul Rahim, N. A., van Noort, D., & Yu, H. (2009) · Lab on a Chip · doi:10.1039/b915147h · Cited by 340

Divergent Routes toward Wnt and R-spondin Niche Independency during Human Gastric Carcinogenesis

Nanki, K., Toshimitsu, K., Takano, A., Fujii, M., Shimokawa, M., Ohta, Y., Matano, M., Seino, T., Nishikori, S., Ishikawa, K., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.027 · Cited by 340

Human gastric cancer modelling using organoids

Seidlitz, T., Merker, S. R., Rothe, A., Zakrzewski, F., von Neubeck, C., Grützmann, K., Sommer, U. J., Schweitzer, C., Schölch, S., Uhlemann, H., et al. (2018) · Gut · doi:10.1136/gutjnl-2017-314549 · Cited by 333

Somatic inflammatory gene mutations in human ulcerative colitis epithelium

Nanki, K., Fujii, M., Shimokawa, M., Matano, M., Nishikori, S., Date, S., Takano, A., Toshimitsu, K., Ohta, Y., Takahashi, S., et al. (2019) · Nature · doi:10.1038/s41586-019-1844-5 · Cited by 331

Persistence and Toxin Production by Clostridium difficile within Human Intestinal Organoids Result in Disruption of Epithelial Paracellular Barrier Function

Leslie, J. L., Huang, S., Opp, J. S., Nagy, M. S., Kobayashi, M., Young, V. B., & Spence, J. R. (2014) · Infection and Immunity · doi:10.1128/iai.02561-14 · Cited by 330

DNA Methylation and Transcription Patterns in Intestinal Epithelial Cells From Pediatric Patients With Inflammatory Bowel Diseases Differentiate Disease Subtypes and Associate With Outcome

Howell, K. J., Kraiczy, J., Nayak, K., Gasparetto, M., Ross, A., Lee, C., Mak, T. N., Koo, B., Kumar, N., Lawley, T. D., et al. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.10.007 · Cited by 329

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

Koike, H., Iwasawa, K., Ouchi, R., Maezawa, M., Giesbrecht, K., Saiki, N., Ferguson, A., Kimura, M., Thompson, W. L., Wells, J. M., et al. (2019) · Nature · doi:10.1038/s41586-019-1598-0 · Cited by 325

Epigenetic resetting of human pluripotency

Guo, G., von Meyenn, F., Rostovskaya, M., Clarke, J., Dietmann, S., Baker, D., Sahakyan, A., Myers, S., Bertone, P., Reik, W., et al. (2017) · Development · doi:10.1242/dev.146811 · Cited by 324

Dishing out mini-brains: Current progress and future prospects in brain organoid research

Kelava, I., & Lancaster, M. A. (2016) · Developmental Biology · doi:10.1016/j.ydbio.2016.06.037 · Cited by 323

Pluripotent stem cell-derived organoids: using principles of developmental biology to grow human tissues in a dish

McCauley, H. A., & Wells, J. M. (2017) · Development · doi:10.1242/dev.140731 · Cited by 322

Differentiated human airway organoids to assess infectivity of emerging influenza virus

Zhou, J., Li, C., Sachs, N., Chiu, M. C., Wong, B. H., Chu, H., Poon, V. K., Wang, D., Zhao, X., Wen, L., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1806308115 · Cited by 316

Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics

Li, X., Francies, H. E., Secrier, M., Perner, J., Miremadi, A., Galeano-Dalmau, N., Barendt, W. J., Letchford, L., Leyden, G. M., Goffin, E. K., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05190-9 · Cited by 316

Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis

Berkers, G., van Mourik, P., Vonk, A. M., Kruisselbrink, E., Dekkers, J. F., de Winter-de Groot, K. M., Arets, H. G. M., Marck-van der Wilt, R. E. P., Dijkema, J. S., Vanderschuren, M. M., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.01.068 · Cited by 310

Human embryonic stem cells: research, ethics and policy

de Wert, G. M. W. R. (2003) · Human Reproduction · doi:10.1093/humrep/deg143 · Cited by 301

Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids

Sampaziotis, F., Justin, A. W., Tysoe, O. C., Sawiak, S., Godfrey, E. M., Upponi, S. S., Gieseck, R. L., de Brito, M. C., Berntsen, N. L., Gómez-Vázquez, M. J., et al. (2017) · Nature Medicine · doi:10.1038/nm.4360 · Cited by 296

Growth of Epithelial Organoids in a Defined Hydrogel

Broguiere, N., Isenmann, L., Hirt, C., Ringel, T., Placzek, S., Cavalli, E., Ringnalda, F., Villiger, L., Züllig, R., Lehmann, R., et al. (2018) · Advanced Materials · doi:10.1002/adma.201801621 · Cited by 282

Stepwise differentiation of pluripotent stem cells into retinal cells

Osakada, F., Ikeda, H. O., Sasai, Y., & Takahashi, M. (2009) · Nature Protocols · doi:10.1038/nprot.2009.51 · Cited by 269

A novel human gastric primary cell culture system for modelling Helicobacter pylori infection in vitro

Schlaermann, P., Toelle, B., Berger, H., Schmidt, S. C., Glanemann, M., Ordemann, J., Bartfeld, S., Mollenkopf, H., & Meyer, T. F. (2014) · Gut · doi:10.1136/gutjnl-2014-307949 · Cited by 264

Organoid and Assembloid Technologies for Investigating Cellular Crosstalk in Human Brain Development and Disease

Marton, R. M., & Pașca, S. P. (2019) · Trends in Cell Biology · doi:10.1016/j.tcb.2019.11.004 · Cited by 253

Wnt/β-catenin promotes gastric fundus specification in mice and humans

McCracken, K. W., Aihara, E., Martin, B., Crawford, C. M., Broda, T. R., Tréguier, J., Zhang, X., Shannon, J. M., Montrose, M. H., & Wells, J. M. (2017) · Nature · doi:10.1038/nature21021 · Cited by 222

Human iPSC banking: barriers and opportunities

Huang, C., Liu, C.-L., Ting, C.-Y., Chiu, Y.-T., Cheng, Y., Nicholson, M. W., & Hsieh, P. C. H. (2019) · Journal of Biomedical Science · doi:10.1186/s12929-019-0578-x · Cited by 222

Pooled In Vitro and In Vivo CRISPR-Cas9 Screening Identifies Tumor Suppressors in Human Colon Organoids

Michels, B. E., Mosa, M. H., Streibl, B. I., Zhan, T., Menche, C., Abou-El-Ardat, K., Darvishi, T., Członka, E., Wagner, S., Winter, J., et al. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.04.003 · Cited by 222

Alterations in the epithelial stem cell compartment could contribute to permanent changes in the mucosa of patients with ulcerative colitis

Dotti, I., Mora‐Buch, R., Ferrer-Picón, E., Planell, N., Jung, P., Masamunt, M. C., Leal, R. F., de Carpi, J. M., Llach, J., Ordás, Í., et al. (2016) · Gut · doi:10.1136/gutjnl-2016-312609 · Cited by 207

Human Fetal TNF-α-Cytokine-Producing CD4+ Effector Memory T Cells Promote Intestinal Development and Mediate Inflammation Early in Life

Schreurs, R., Baumdick, M. E., Sagebiel, A. F., Kaufmann, M., Mokrý, M., Klarenbeek, P. L., Schaltenberg, N., Steinert, F. L., van Rijn, J. M., Drewniak, A., et al. (2019) · Immunity · doi:10.1016/j.immuni.2018.12.010 · Cited by 206

Zika-Virus-Encoded NS2A Disrupts Mammalian Cortical Neurogenesis by Degrading Adherens Junction Proteins

Yoon, K., Song, G., Qian, X., Pan, J., Xu, D., Rho, H.-S., Kim, N.-S., Habela, C. W., Zheng, L., Jacob, F., et al. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.07.014 · Cited by 206

Human kidney organoids: progress and remaining challenges

Nishinakamura, R. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0176-x · Cited by 205

Genome-Scale CRISPR Screening in Human Intestinal Organoids Identifies Drivers of TGF-β Resistance

Ringel, T., Frey, N., Ringnalda, F., Janjuha, S., Cherkaoui, S., Butz, S., Srivatsa, S., Pirkl, M., Russo, G., Villiger, L., et al. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.02.007 · Cited by 202

Validated germline-competent embryonic stem cell lines from nonobese diabetic mice

Nichols, J., Jones, K. D., Phillips, J. M., Newland, S. A., Roode, M., Mansfield, W., Smith, A. G., & Cooke, A. (2009) · Nature Medicine · doi:10.1038/nm.1996 · Cited by 201

Modeling rotavirus infection and antiviral therapy using primary intestinal organoids

Yin, Y., Bijvelds, M. J. C., Dang, W., Xu, L., van der Eijk, A. A., Knipping, K., Tüysüz, N., Dekkers, J. F., Wang, Y., de Jonge, J., et al. (2015) · Antiviral Research · doi:10.1016/j.antiviral.2015.09.010 · Cited by 196

Co-culture with intestinal epithelial organoids allows efficient expansion and motility analysis of intraepithelial lymphocytes

Nozaki, K., Mochizuki, W., Matsumoto, Y., Matsumoto, T., Fukuda, M., Mizutani, T., Watanabe, M., & Nakamura, T. (2016) · Journal of Gastroenterology · doi:10.1007/s00535-016-1170-8 · Cited by 188

DNA methylation defines regional identity of human intestinal epithelial organoids and undergoes dynamic changes during development

Kraiczy, J., Nayak, K., Howell, K. J., Ross, A., Forbester, J. L., Salvestrini, C., Mustata, R. C., Perkins, S., Andersson-Rolf, A., Leenen, E., et al. (2017) · Gut · doi:10.1136/gutjnl-2017-314817 · Cited by 188

Epidemiology of human noroviruses and updates on vaccine development

Ramani, S., Atmar, R. L., & Estes, M. K. (2013) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000000022 · Cited by 181

Expansion of Adult Human Pancreatic Tissue Yields Organoids Harboring Progenitor Cells with Endocrine Differentiation Potential

Loomans, C. J. M., Williams, N. A., Balak, J. R. A., Ringnalda, F. C. A. S., van Gurp, L., Huch, M., Boj, S. F., Sato, T., Kester, L. A., Lopes, S. M. C. D. S., et al. (2018) · Stem Cell Reports · doi:10.1016/j.stemcr.2018.02.005 · Cited by 175

PEG-4MAL hydrogels for human organoid generation, culture, and in vivo delivery

Cruz-Acuña, R., Quirós, M., Huang, S., Siuda, D., Spence, J. R., Nusrat, A., & García, A. J. (2018) · Nature Protocols · doi:10.1038/s41596-018-0036-3 · Cited by 168

Esophageal Organoids from Human Pluripotent Stem Cells Delineate Sox2 Functions during Esophageal Specification

Trisno, S. L., Philo, K. E. D., McCracken, K. W., Catá, E. M., Ruiz-Torres, S., Rankin, S. A., Han, L., Nasr, T., Chaturvedi, P., Rothenberg, M. E., et al. (2018) · Cell stem cell · doi:10.1016/j.stem.2018.08.008 · Cited by 152

The emergence of influenza A H7N9 in human beings 16 years after influenza A H5N1: a tale of two cities

To, K. K., Chan, J. F., Chen, H., Li, L., & Yuen, K. (2013) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(13)70167-1 · Cited by 148

Quantification of regenerative potential in primary human mammary epithelial cells

Linnemann, J. R., Miura, H., Meixner, L. K., Irmler, M., Kloos, U. J., Hirschi, B., Bartsch, H. S., Sass, S., Beckers, J., Theis, F. J., et al. (2015) · Development · doi:10.1242/dev.123554 · Cited by 146

Stem Cells, Genome Editing, and the Path to Translational Medicine

Soldner, F., & Jaenisch, R. (2018) · Cell · doi:10.1016/j.cell.2018.09.010 · Cited by 144

Large scale genetics in a small vertebrate, the zebrafish

Haffter, P., & Nüsslein‐Volhard, C. (1996) · The International Journal of Developmental Biology · doi:10.1387/ijdb.8735932 · Cited by 138

A Primary Human Macrophage-Enteroid Co-Culture Model to Investigate Mucosal Gut Physiology and Host-Pathogen Interactions

Baetz, N. W., Noel, G., Staab, J. F., Donowitz, M., Kovbasnjuk, O. N., Pasetti, M. F., & Zachos, N. C. (2017) · Gastroenterology · doi:10.1016/s0016-5085(17)30545-0 · Cited by 126

Systematic Identification of Culture Conditions for Induction and Maintenance of Naive Human Pluripotency

Theunissen, T. W., Powell, B. E., Wang, H., Mitalipova, M., Faddah, D. A., Reddy, J., Fan, Z. P., Maetzel, D., Ganz, K., Shi, L., et al. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.09.003 · Cited by 123

Modeling infectious diseases and host-microbe interactions in gastrointestinal organoids

Bartfeld, S. (2016) · Developmental Biology · doi:10.1016/j.ydbio.2016.09.014 · Cited by 116

Mechanically and chemically defined hydrogel matrices for patient-derived colorectal tumor organoid culture

Ng, S., Tan, W. J., Pek, M. M. X., Tan, M.-H., & Kurisawa, M. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.119400 · Cited by 105

The worm in us – Caenorhabditis elegans as a model of human disease

Baumeister, R., & Ge, L. (2002) · Trends in biotechnology · doi:10.1016/s0167-7799(01)01925-4 · Cited by 100

Mesenchymal Stem Cells Increase Alveolar Differentiation in Lung Progenitor Organoid Cultures

Leeman, K. T., Pessina, P., Lee, J., & Kim, C. F. (2019) · Scientific Reports · doi:10.1038/s41598-019-42819-1 · Cited by 99

3D Modeling of Esophageal Development using Human PSC-Derived Basal Progenitors Reveals a Critical Role for Notch Signaling

Zhang, Y., Yang, Y., Jiang, M. Z., Huang, S. X. L., Zhang, W., Alam, D. A., Danopoulos, S., Mori, M., Chen, Y., Balasubramanian, R., et al. (2018) · Cell stem cell · doi:10.1016/j.stem.2018.08.009 · Cited by 98

The zebrafish issue ofDevelopment

Nüsslein‐Volhard, C. (2012) · Development · doi:10.1242/dev.085217 · Cited by 97

A critical look: Challenges in differentiating human pluripotent stem cells into desired cell types and organoids

Fowler, J. L., Ang, L. T., & Loh, K. M. (2019) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.368 · Cited by 87

Single cell analysis of Crohn’s disease patient-derived small intestinal organoids reveals disease activity-dependent modification of stem cell properties

Suzuki, K., Murano, T., Shimizu, H., Ito, G., Nakata, T., Fujii, S., Ishibashi, F., Kawamoto, A., Anzai, S., Kuno, R., et al. (2018) · Journal of Gastroenterology · doi:10.1007/s00535-018-1437-3 · Cited by 84

One-step generation of conditional and reversible gene knockouts

Andersson-Rolf, A., Mustata, R. C., Merenda, A., Kim, J., Perera, S., Grego, T., Andrews, K., Tremble, K., Silva, J., Fink, J., et al. (2017) · Nature Methods · doi:10.1038/nmeth.4156 · Cited by 83

Organoid models for translational pancreatic cancer research

Tiriac, H., Plenker, D., Baker, L. A., & Tuveson, D. A. (2019) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2019.02.003 · Cited by 81

Development of Collagen-Based 3D Matrix for Gastrointestinal Tract-Derived Organoid Culture

Jee, J. H., Lee, D. H., Ko, J., Hahn, S., Jeong, S. Y., Kim, H. K., Park, E., Choi, S. Y., Jeong, S., Lee, J. W., et al. (2019) · Stem Cells International · doi:10.1155/2019/8472712 · Cited by 80

Genome-wide RNAi screens in Caenorhabditis elegans: impact on cancer research

Poulin, G. B., Nandakumar, R., & Ahringer, J. (2004) · Oncogene · doi:10.1038/sj.onc.1208010 · Cited by 68

Patient-Derived Colorectal Cancer Organoids Upregulate Revival Stem Cell Marker Genes following Chemotherapeutic Treatment

Engel, R. M., Chan, W. H., Nickless, D. K., Hlavca, S., Richards, E., Kerr, G., Oliva, K., McMurrick, P. J., Jardé, T., & Abud, H. E. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9010128 · Cited by 59

Systematic Identification of Culture Conditions for Induction and Maintenance of Naive Human Pluripotency

Theunissen, T. W., Powell, B. E., Wang, H., Mitalipova, M., Faddah, D. A., Reddy, J., Fan, Z. P., Maetzel, D., Ganz, K., Shi, L., et al. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.08.002 · Cited by 52

Gene Targeting in Human Pluripotent CellsPreprint

Hockemeyer, D. F., & Jaenisch, R. (2010) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2010.75.021 · Cited by 51

Predictability of Metabolism of Ibuprofen and Naproxen Using Chimeric Mice with Human Hepatocytes

Sanoh, S., Horiguchi, A., Sugihara, K., Kotake, Y., Tayama, Y., Uramaru, N., Ohshita, H., Tateno, C., Horie, T., Kitamura, S., et al. (2012) · Drug Metabolism and Disposition · doi:10.1124/dmd.112.047555 · Cited by 47

Understanding the role of steroids in typical and atypical brain development: Advantages of using a “brain in a dish” approach

Adhya, D., Annuario, E., Lancaster, M. A., Price, J., Baron‐Cohen, S., & Srivastava, D. P. (2017) · Journal of Neuroendocrinology · doi:10.1111/jne.12547 · Cited by 45

Patient-derived organoids (PDOs) as a novel in vitro model for neuroblastoma tumours

Fusco, P., Parisatto, B., Rampazzo, E., Persano, L., Frasson, C., Meglio, A. D., Leslz, A., Santoro, L., Cafferata, B., Zin, A., et al. (2019) · BMC Cancer · doi:10.1186/s12885-019-6149-4 · Cited by 43

CYP2C9-Catalyzed Metabolism of S-Warfarin to 7-Hydroxywarfarin in Vivo and in Vitro in Chimeric Mice with Humanized Liver

Inoue, T., Nitta, K., Sugihara, K., Horie, T., Kitamura, S., & Ohta, S. (2008) · Drug Metabolism and Disposition · doi:10.1124/dmd.108.022830 · Cited by 38

Engineering organoids

Hofer, M., & Lutolf, M. P. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00279-y · Cited by 1,184

Organoids

Zhao, Z., Chen, X., Dowbaj, A. M., Sljukic, A., Bratlie, K., Lin, L., Fong, E. L. S., Balachander, G. M., Chen, Z., Soragni, A., et al. (2022) · Nature Reviews Methods Primers · doi:10.1038/s43586-022-00174-y · Cited by 1,082

Nanodelivery of nucleic acids

Mendes, B. B., Conniot, J., Avital, A., Yao, D., Jiang, X., Zhou, X., Sharf-Pauker, N., Xiao, Y., Adir, O., Liang, H., et al. (2022) · Nature Reviews Methods Primers · doi:10.1038/s43586-022-00104-y · Cited by 719

Induced pluripotent stem cells (iPSCs): molecular mechanisms of induction and applications

Cerneckis, J., Cai, H., & Shi, Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01809-0 · Cited by 452

Towards organoid culture without Matrigel

Kozlowski, M. T., Crook, C. J., & Ku, H. T. (2021) · Communications Biology · doi:10.1038/s42003-021-02910-8 · Cited by 409

Organoids As Promising Tools In Therapy

Shravani, P. S. D. K. (2023) · Zenodo (CERN European Organization for Nuclear Research) · doi:10.5281/zenodo.8278935

New developments and applications of human organoids

Andersson-Rolf, A., & Clevers, H. C. (2026) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-026-00974-0 · Cited by 25

Clinical applications of human organoids

Verstegen, M. M. A., Coppes, R. P., Béghin, A., Coppi, P. D., Gerli, M., de Graeff, N., Pan, Q., Saito, Y., Shi, S., ZADPOOR, A. A., et al. (2025) · Nature Medicine · doi:10.1038/s41591-024-03489-3 · Cited by 230

Human organoids: a new dimension in cell biology

Lehmann, R., Lee, C. M., Shugart, E. C., Benedetti, M., Charo, R. A., Gartner, Z. J., Hogan, B. L. M., Knoblich, J. A., Nelson, C. M., & Wilson, K. (2019) · Molecular Biology of the Cell · doi:10.1091/mbc.e19-03-0135 · Cited by 158

The organoid cell atlas

the Human Cell Atlas ‘Biological Network’ Organoids, Bock, C., Boutros, M., Camp, J. G., Clarke, L., Clevers, H., Knoblich, J. A., Liberali, P., Regev, A., Rios, A. C., et al. (2021) · Nature Biotechnology · doi:10.1038/s41587-020-00762-x · Cited by 171