Intestinal Organoids

The intestinal epithelium is a rapidly renewing tissue that can undergo complete cellular replacement every four to five days. These regenerative properties make the intestinal epithelium an attractive system for researchers studying epithelial regeneration, adult stem cell biology, disease modelling and cancer biology, both within and outside the context of the intestine.

Explore the resources below for information to support your intestinal research and the growth of intestinal organoids.

Key Applications of Intestinal Organoids

PSC-Derived Intestinal Organoids

Spence JR et al. (2011) Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 470(7332): 105–9.
Múnera JO et al. (2017) Generation of GastroIntestinal Organoids from Human Pluripotent Stem Cells. Methods Mol Biol 1597: 167–177.

Intestinal Cell Biology

de Jong PR et al. (2016) ERK5 signaling rescues intestinal epithelial turnover and tumour cell proliferation upon ERK1/2 abrogation. Nat Commun 7: 11551.
Dotti I et al. (2016) Alterations in the epithelial stem cell compartment could contribute to permanent changes in the mucosa of patients with ulcerative colitis. Gut. Epub ahead of print, DOI: 10.1136/gutjnl-2016-312609.
Igarashi M & Guarente L. (2016) mTORC1 and SIRT1 cooperate to foster expansion of gut adult stem cells during calorie restriction. Cell 166(2): 436–50.
Oudhoff MJ et al. (2016) SETD7 controls intestinal regeneration and tumorigenesis by regulating Wnt/β-catenin and Hippo/YAP signaling. Dev Cell 37(1): 47–57.
Sasaki N et al. (2016) Reg4+ deep crypt secretory cells function as epithelial niche for Lgr5+ stem cells in colon. Proc Natl Acad Sci U S A 113(37): E5399-407.
Schewe M et al. (2016) Secreted phospholipases A2 are intestinal stem cell niche factors with distinct roles in homeostasis, inflammation, and cancer. Cell Stem Cell 19(1): 38–51.
Workman MJ et al. (2017) Engineered Human Pluripotent-Stem-Cell-Derived Intestinal Tissues with a Functional Enteric Nervous System. Nat Med 23(1): 49–59.
Zietek T et al. (2015) Intestinal organoids for assessing nutrient transport, sensing and incretin secretion. Sci Rep 5: 16831.
Mohanan V et al. (2018) C1orf106 is a Colitis Risk Gene That Regulates Stability of Epithelial Adherens Junctions. Science 359(6380): 1161–1166.
Wang B et al. (2018) Phospholipid Remodeling and Cholesterol Availability Regulate Intestinal Stemness and Tumorigenesis. Cell Stem Cell 22(2): 206–220.
Wichert R et al. (2017) Mucus Detachment by Host Metalloprotease Meprin Β Requires Shedding of its Inactive Pro-form, Which is abrogated by the Pathogenic Protease RgpB. Cell Rep 21(8): 2090–2103.
Haber AL et al. (2017) A Single-Cell Survey of the Small Intestinal Epithelium. Nature 551(7680): 333–339.
Kraiczy J et al. (2017) DNA Methylation Defines Regional Identity of Human Intestinal Epithelial Organoids and Undergoes Dynamic Changes During Development. Gut.
Zhou W et al. (2018) Glucose Stimulates Intestinal Epithelial Crypt Proliferation by Modulating Cellular Energy Metabolism. J Cell Physiol 233(4): 3465–3475.
Hahn S et al. (2017) Organoid-Based Epithelial to Mesenchymal Transition (OEMT) Model: From an Intestinal Fibrosis Perspective. Sci Rep 7(1): 2435.
Rong S et al. (2017) Cholesterol Auxotrophy and Intolerance to Ezetimibe in Mice with SREBP-2 Deficiency in the Intestine. J Lipid Res 58(10): 1988–1998.
Morgenstern Y et al. (2017) Casein Kinase 1-Epsilon Or 1-Delta Required for Wnt-Mediated Intestinal Stem Cell Maintenance. Embo J 36(20): 3046–3061.
Kraft CL et al. (2017) GUCY2C Maintains Intestinal Lgr5+ Stem Cells by Opposing ER Stress. Oncotarget 8(61): 102923–102933.

Cancer Research

Borovski T et al. (2017) Inhibition of RAF1 Kinase activity Restores Apicobasal Polarity and Impairs Tumour Growth in Human Colorectal Cancer. Gut 66(6): 1106–1115.
Fernández-Majada V et al. (2016) The Tumour Suppressor CYLD Regulates the p53 DNA Damage Response. Nat Commun 7: 12508.
Fujii M et al. (2016) A Colorectal Tumor Organoid Library Demonstrates Progressive Loss of Niche Factor Requirements During Tumorigenesis. Cell Stem Cell 18(6): 827–38.
Liu W et al. (2016) Olfactomedin 4 Deletion Induces Colon Adenocarcinoma in ApcMin/+ Mice. Oncogene 35(40): 5237–5247.
van der Heijden M et al. (2016)
Bcl-2 is a Critical Mediator of Intestinal Transformation. Nat Commun 7: 10916.
Yan HHN et al. (2017) Rnf43 Germline and Somatic Mutation in Serrated Neoplasia Pathway and its Association with BRAF Mutation. Gut 66(9): 1645–1656.
Yum MK et al. (2016) AIMP2 Controls Intestinal Stem Cell Compartments and Tumorigenesis by Modulating Wnt/β-Catenin Signaling. Cancer Res 76(15): 4559–68.
Duhachek-Muggy S et al. (2017) Growth Differentiation Factor 11 Does Not Mitigate the Lethal Effects of Total-Abdominal Irradiation. Radiat Res 188(5): 469–475.
Karki R et al. (2016) Nlrc3 is an inhibitory Sensor of PI3K-mTOR Pathways in Cancer. Nature 540: 583–587.
Dame MK et al. (2018) Identification, Isolation and Characterization of Human Lgr5-positive Colon Adenoma Cells. Development 145(6).
Tauriello DVF et al. (2018) Tgfβ Drives Immune Evasion in Genetically Reconstituted Colon Cancer Metastasis. Nature 554(7693): 538–543.
Roper J et al. (2018) Colonoscopy-Based Colorectal Cancer Modeling in Mice with CRISPR-Cas9 Genome Editing and Organoid Transplantation. Nat Protoc 13(2): 217–234.
Fumagalli A et al. (2018) A Surgical Orthotopic Organoid Transplantation Approach in Mice to Visualize and Study Colorectal Cancer Progression. Nat Protoc 13(2): 235–247.
Regan JL et al. (2017) Non-Canonical Hedgehog Signaling is a Positive Regulator of the Wnt Pathway and is Required for the Survival of Colon Cancer Stem Cells. Cell Rep 21(10): 2813–2828.
Novellasdemunt L et al. (2017) USP7 is a Tumor-Specific Wnt activator for APC-Mutated Colorectal Cancer by Mediating β-Catenin Deubiquitination. Cell Rep 21(3): 612–627.
Banerjee A et al. (2016) Endoplasmic Reticulum Stress and IRE-1 Signaling Cause Apoptosis in Colon Cancer Cells in Response to Andrographolide Treatment. Oncotarget 7(27): 41432–41444.
Liu W et al. (2016) Olfactomedin 4 Deletion Induces Colon Adenocarcinoma in ApcMin/+ Mice. Oncogene 35(40): 5237–5247.

Precision Medicine Screening

Vlachogiannis G et al. (2018) Patient-Derived Organoids Model Treatment Response of Metastatic GastroIntestinal Cancers. Science 359(6378): 920–926.
Beekman JM. (2016) Individualized Medicine Using Intestinal Responses to CFTR Potentiators and Correctors. Pediatr Pulmonol 51(S44): S23–S34.
Hagemeijer MC et al. (2018) Translational Research to Enable Personalized Treatment of Cystic Fibrosis. J Cyst Fibros 17(2s): S46–S51.

Therapeutic Development

Intestinal Immunity and Inflammation

Gerbe F et al. (2016) Intestinal Epithelial Tuft Cells Initiate Type 2 Mucosal Immunity to Helminth Parasites. Nature 529(7585): 226–30.
Ibiza S et al. (2016) Glial-Cell-Derived Neuroregulators Control Type 3 Innate Lymphoid Cells and Gut Defence. Nature 535(7612): 440–443.
Lindemans CA et al. (2015) Interleukin-22 Promotes Intestinal-Stem-Cell-Mediated Epithelial Regeneration. Nature 528(7583): 560–564.
Oancea I et al. (2017) Colonic Microbiota Can Promote Rapid Local Improvement of Murine Colitis by Thioguanine Independently of T Lymphocytes and Host Metabolism. Gut 66(1): 59–69.
Peuker K et al. (2016) Epithelial Calcineurin Controls Microbiota-Dependent Intestinal Tumor Development. Nat Med 22(5): 506–15.
Wang Y et al. (2017) An LGG-Derived Protein Promotes IgA Production Through Upregulation of APRIL Expression in Intestinal Epithelial Cells. Mucosal Immunol 10(2): 373–384.
Wilson SS et al. (2015) A Small Intestinal Organoid Model of Non-Invasive Enteric Pathogen-Epithelial Cell Interactions. Mucosal Immunol 8(2): 352–61.
Van Opdenbosch N et al. (2017) Caspase-1 Engagement and TLR-induced C-FLIP Expression Suppress ASC/Caspase-8-Dependent Apoptosis by Inflammasome Sensors Nlrp1b and NLRC4. Cell Rep 21(12): 3427–3444.
Howell KJ et al. (2018) DNA Methylation and Transcription Patterns in Intestinal Epithelial Cells from Pediatric Patients with Inflammatory Bowel Diseases Differentiate Disease Subtypes and Associate with Outcome. Gastroenterology 154(3): 585–598.
Schwerd T et al. (2018) Nox1 Loss-of-Function Genetic Variants in Patients with Inflammatory Bowel Disease. Mucosal Immunol 11(2): 562–574.
Aladegbami B et al. (2017) Epithelial Cell Specific Raptor is Required for Initiation of Type 2 Mucosal Immunity in Small Intestine. Sci Rep 7(1): 5580.
Bhushal S et al. (2017) Cell Polarization and Epigenetic Status Shape the Heterogeneous Response to Type III interferons in Intestinal Epithelial Cells. Front Immunol 8: 671.
Sharma D et al. (2018) Pyrin Inflammasome Regulates Tight Junction Integrity to Restrict Colitis and Tumorigenesis. Gastroenterology 154(4): 948–964.

Microbiomics and Microbial Pathogenesis

Bartfeld S. (2016) Modeling Infectious Diseases and Host-Microbe Interactions in Gastrointestinal Organoids. Dev Biol 420(2): 262–270.
In Jg et al. (2016) Human Mini-Guts: New Insights Into Intestinal Physiology and Host-Pathogen Interactions. Nat Rev Gastroenterol Hepatol 13(11): 633–642.
Tao L et al. (2016) Frizzled Proteins are Colonic Epithelial Receptors for C. difficile Toxin B. Nature 538(7625): 350–355.
Wang J et al. (2018) Ceragenin CSA13 Reduces Clostridium difficile Infection in Mice by Modulating the Intestinal Microbiome and Metabolites. Gastroenterology 154(6): 1737–1750.
Leber A et al. (2018) NLRX1 Modulates Immunometabolic Mechanisms Controlling the Host-gut Microbiota Interactions During Inflammatory Bowel Disease. Front Immunol 9: 363.
Burger E et al. (2018) Loss of Paneth Cell Autophagy Causes Acute Susceptibility to Toxoplasma Gondii-Mediated Inflammation. Cell Host Microbe 23(2): 177–190.
Zhang D et al. (2017) Human Intestinal Organoids Express Histo-Blood Group Antigens, Bind Norovirus VLPs, and Support Limited Norovirus Replication. Sci Rep 7(1): 12621.
Yahiro K et al. (2018) Mechanism of Inhibition of Shiga-Toxigenic Escherichia coli SubAB Cytotoxicity by Steroids and Diacylglycerol Analogues. Cell Death Discov 4: 22.
Entwistle LJ et al. (2017) Epithelial-Cell-Derived Phospholipase A2 Group 1B is an Endogenous Anthelmintic. Cell Host Microbe 22(4): 484–493.
Dhawan S et al. (2016) Acetylcholine-Producing T Cells in the Intestine Regulate Antimicrobial Peptide Expression and Microbial Diversity. Am J Physiol Gastrointest Liver Physiol 311(5): G920–G933.
Wang Y et al. (2017) The Intestinal Microbiota Regulates Body Composition Through NFIL3 and the Circadian Clock. Science 357(6354): 912–916.