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

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

Spatial reconstruction of single-cell gene expression data

Satija, R., Farrell, J. A., Gennert, D., Schier, A. F., & Regev, A. (2015) · Nature Biotechnology · doi:10.1038/nbt.3192 · Cited by 7,055

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

Modeling Development and Disease with Organoids

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

Batch effects in single-cell RNA-sequencing data are corrected by matching mutual nearest neighbors

Haghverdi, L., Lun, A. T. L., Morgan, M. D., & Marioni, J. C. (2018) · Nature Biotechnology · doi:10.1038/nbt.4091 · Cited by 2,416

A single-cell survey of the small intestinal epithelium

Haber, A. L., Biton, M., Rogel, N., Herbst, R. H., Shekhar, K., Smillie, C., Burgin, G., Delorey, T. M., Howitt, M. R., Katz, Y., et al. (2017) · Nature · doi:10.1038/nature24489 · Cited by 1,750

Activation and signaling of the p38 MAP kinase pathway

Zarubin, T., & Han, J. (2005) · Cell Research · doi:10.1038/sj.cr.7290257 · Cited by 1,711

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

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

Insulin-like growth factors and neoplasia

Pollak, M., Schernhammer, E. S., & Hankinson, S. E. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1387 · Cited by 1,477

Diffusion pseudotime robustly reconstructs lineage branching

Haghverdi, L., Büttner, M., Wolf, F. A., Buettner, F., & Theis, F. J. (2016) · Nature Methods · doi:10.1038/nmeth.3971 · Cited by 1,385

Single-cell messenger RNA sequencing reveals rare intestinal cell types

Grün, D., Lyubimova, A., Kester, L., Wiebrands, K., Basak, O., Sasaki, N., Clevers, H., & van Oudenaarden, A. (2015) · Nature · doi:10.1038/nature14966 · Cited by 1,234

Reference component analysis of single-cell transcriptomes elucidates cellular heterogeneity in human colorectal tumors

Li, H., Courtois, E. T., Sengupta, D., Tan, Y., Chen, K. H., Goh, J. J. L., Kong, S. L., Chua, C., Hon, L. K., Tan, W. S., et al. (2017) · Nature Genetics · doi:10.1038/ng.3818 · Cited by 1,080

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 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

Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and adults: relation to age, sex, stage of puberty, testicular size, and body mass index

Juul, A., Bang, P., Hertel, N. T., Main, K., Dalgaard, P., Jørgensen, K., Müller, J., Hall, K. E., & Skakkebaek, N. E. (1994) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.78.3.744 · Cited by 773

Visualization and targeting of LGR5+ human colon cancer stem cells

Shimokawa, M., Ohta, Y., Nishikori, S., Matano, M., Takano, A., Fujii, M., Date, S., Sugimoto, S., Kanai, T., & Sato, T. (2017) · Nature · doi:10.1038/nature22081 · Cited by 728

destiny : diffusion maps for large-scale single-cell data in R

Angerer, P., Haghverdi, L., Büttner, M., Theis, F. J., Marr, C., & Buettner, F. (2016) · Bioinformatics · doi:10.1093/bioinformatics/btv715 · Cited by 640

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

Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal

Yan, K. S., Janda, C. Y., Chang, J., Zheng, G. X. Y., Larkin, K. A., Luca, V. C., Chia, L. A., Mah, A. T., Han, A. S., Terry, J. M., et al. (2017) · Nature · doi:10.1038/nature22313 · Cited by 463

Induced Quiescence of Lgr5+ Stem Cells in Intestinal Organoids Enables Differentiation of Hormone-Producing Enteroendocrine Cells

Başak, O., Beumer, J., Wiebrands, K., Seno, H., van Oudenaarden, A., & Clevers, H. C. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.11.001 · Cited by 365

Efficient genetic engineering of human intestinal organoids using electroporation

Fujii, M., Matano, M., Nanki, K., & Sato, T. (2015) · Nature Protocols · doi:10.1038/nprot.2015.088 · Cited by 364

Growth Factor FGF2 Cooperates with Interleukin-17 to Repair Intestinal Epithelial Damage

Song, X., Dai, D., He, X., Zhu, S., Yao, Y., Gao, H., Wang, J., Qu, F., Qiu, J., Wang, H., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.06.024 · Cited by 249

The Ets transcription factor Spi-B is essential for the differentiation of intestinal microfold cells

Kanaya, T., Hase, K., Takahashi, D., Fukuda, S., Hoshino, K., Sasaki, I., Hemmi, H., Knoop, K. A., Kumar, N., Sato, M., et al. (2012) · Nature Immunology · doi:10.1038/ni.2352 · Cited by 228

Active and water-soluble form of lipidated Wnt protein is maintained by a serum glycoprotein afamin/α-albumin

Mihara, E., Hirai, H., Yamamoto, H., Tamura‐Kawakami, K., Matano, M., Kikuchi, A., Sato, T., & Takagi, J. (2016) · eLife · doi:10.7554/elife.11621 · Cited by 203

FGF-2 enhances intestinal stem cell survival and its expression is induced after radiation injury

Houchen, C. W., George, R. J., Sturmoski, M., & Cohn, S. M. (1999) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1999.276.1.g249 · Cited by 136

Impact of Diet-Induced Obesity on Intestinal Stem Cells: Hyperproliferation but Impaired Intrinsic Function That Requires Insulin/IGF1

Mah, A. T., Landeghem, L. V., Gavin, H. E., Magness, S. T., & Lund, P. K. (2014) · Endocrinology · doi:10.1210/en.2014-1112 · Cited by 112

Canonical Wnt signals combined with suppressed TGFβ/BMP pathways promote renewal of the native human colonic epithelium

Reynolds, A. G., Wharton, N., Parris, A., Mitchell, E. M., Sobolewski, A., Kam, C., Bigwood, L., Hadi, A. E., Münsterberg, A., Lewis, M. S., et al. (2013) · Gut · doi:10.1136/gutjnl-2012-304067 · Cited by 111

p38 kinase regulates epidermal growth factor receptor downregulation and cellular migration

Frey, M. R., Dise, R. S., Edelblum, K. L., & Polk, D. B. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601457 · Cited by 109

Distinct Effects of p38α Deletion in Myeloid Lineage and Gut Epithelia in Mouse Models of Inflammatory Bowel Disease

Otsuka, M., Kang, Y. J., Ren, J., Jiang, H., Wang, Y., Omata, M., & Han, J. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.01.005 · Cited by 107

Ghrelin and Motilin Are Cosecreted from a Prominent Endocrine Cell Population in the Small Intestine

Wierup, N., Björkqvist, M., Weström, B. R., Pierzynowski, S. G., Sundler, F., & Sjölund, K. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-2756 · Cited by 99

‘Cold shock’ increases the frequency of homology directed repair gene editing in induced pluripotent stem cells

Guo, Q. J., Mintier, G. A., Ma-Edmonds, M., Storton, D., Wang, X., Xiao, X., Kienzle, B. K., Zhao, D., & Feder, J. N. (2018) · Scientific Reports · doi:10.1038/s41598-018-20358-5 · Cited by 69

IGF1 stimulates crypt expansion via differential activation of 2 intestinal stem cell populations

Landeghem, L. V., Santoro, M. A., Mah, A. T., Krebs, A. E., Dehmer, J. J., McNaughton, K. K., Helmrath, M. A., Magness, S. T., & Lund, P. K. (2015) · The FASEB Journal · doi:10.1096/fj.14-264010 · Cited by 63

Harnessing single-cell genomics to improve the physiological fidelity of organoid-derived cell types

Mead, B. E., Ordovás-Montañés, J., Braun, A. P., Levy, L. E., Bhargava, P., Szucs, M. J., Ammendolia, D. A., MacMullan, M. A., Yin, X., Hughes, T. K., et al. (2018) · BMC Biology · doi:10.1186/s12915-018-0527-2 · Cited by 50

Gastrointestinal Fibroblasts Have Specialized, Diverse Transcriptional Phenotypes: A Comprehensive Gene Expression Analysis of Human Fibroblasts

Higuchi, Y., Kojima, M., Ishii, G., Aoyagi, K., Sasaki, H., & Ochiai, A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0129241 · Cited by 47

Human organoids: model systems for human biology and medicine

Kim, J., Koo, B.-K., & Knoblich, J. A. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0259-3 · Cited by 2,187

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

Establishment of patient-derived cancer organoids for drug-screening applications

Driehuis, E., Kretzschmar, K., & Clevers, H. C. (2020) · Nature Protocols · doi:10.1038/s41596-020-0379-4 · Cited by 702

Microenvironment drives cell state, plasticity, and drug response in pancreatic cancer

Raghavan, S., Winter, P. S., Navia, A. W., Williams, H. L., DenAdel, A., Lowder, K. E., Galvez-Reyes, J., Kalekar, R. L., Mulugeta, N., Kapner, K. S., et al. (2021) · Cell · doi:10.1016/j.cell.2021.11.017 · Cited by 592

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

A tunable human intestinal organoid system achieves controlled balance between self-renewal and differentiation

Li, Y., Wang, X., Zhou, X., Chen, H., Song, S., Deng, L., Yao, Y., & Yin, X. (2025) · Nature Communications · doi:10.1038/s41467-024-55567-2 · Cited by 58

Visualization of Differentiated Cells in 3D and 2D Intestinal Organoid Cultures

Hanyu, H., Sugimoto, S., & Sato, T. (2023) · Methods in molecular biology · doi:10.1007/978-1-0716-3076-1_12 · Cited by 10

Establishment of 3D Intestinal Organoid Cultures from Intestinal Stem Cells

Sugimoto, S., & Sato, T. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7021-6_7 · Cited by 79

Establishment and Culture of Human Intestinal Organoids Derived from Adult Stem Cells

Pleguezuelos‐Manzano, C., Puschhof, J., van den Brink, S., Geurts, V., Beumer, J., & Clevers, H. C. (2020) · Current Protocols in Immunology · doi:10.1002/cpim.106 · Cited by 277

Exploring the human intestine in a dish: From physiology to disease

Forster, R. E. (2018) · eScholarship (California Digital Library)