@article{93693b2b23e74f9397769d39db1110d5,
title = "Wnt Signaling in 3D: Recent Advances in the Applications of Intestinal Organoids",
abstract = "Intestinal organoids grown from adult stem cells have emerged as prototype 3D organotypic models for studying tissue renewal and homeostasis. Owing to their strict dependence on Wnt signaling, intestinal organoids offer an unprecedented opportunity to examine Wnt pathway regulation in normal physiology and cancer. We review how alterations in growth factor dependency and organoid morphology can be exploited to identify Wnt signaling mechanisms, characterize mutated pathway components, and predict responses of patient-derived tumors to targeted therapy. We discuss current deficits in the understanding of genotype–phenotype relationships that are to be considered when interpreting mutation-induced changes in organoid morphology.",
keywords = "applications, intestinal organoids, mutations, organoid morphology, Wnt pathway",
author = "Alessandra Merenda and Nicola Fenderico and Maurice, {Madelon M.}",
note = "Funding Information: We thank members of the laboratory of M.M.M. for helpful discussions and suggestions. The Oncode Institute is partly financed by the Dutch Cancer Society . This work was supported by European Research Council starting grant 242958 (to M.M.M.), EU FP7 grant Marie Curie ITN 608180 'WntsApp' (to M.M.M.), and the Netherlands Organization for Scientific Research (NWO) VICI grant 91815604 , ECHO grant 711.013.012 , and ZonMW TOP grant 91218050 (to M.M.M.). Adult stem cells multipotent undifferentiated cells that are found throughout the adult body and that retain the ability to self-renew and give rise to all cell types of a specific tissue, which ensures replacement of dying cells and regeneration of damaged tissues. CHIR-99021 (CHIR) an inhibitor of GSK3β kinase, an essential component of the β-catenin destruction complex. Porcupine (Porc) an endoplasmic reticulum (ER)-resident enzyme that modifies Wnt ligands by attaching palmitoleate, a modification essential for their secretion. R/Z DKO double-knockout mutant of the Wnt negative regulator Rnf43 and its homolog Znrf3 . Stem cell niche the microenvironment where adult stem cells reside and receive multiple stimuli from specialized neighboring cells aimed at supporting their growth and maintaining their stemness. Perturbations of such stimuli influence stem cell behavior by promoting either their quiescence, proliferation, or differentiation. Tankyrases poly-ADP-ribosyltransferases that activate the Wnt signaling pathway by mediating poly-ADP-ribosylation of AXIN, a step required for its subsequent degradation. Inhibitors of these enzymes have been developed to reduce Wnt activity levels. Tissue renewal the process by which somatic cells at the end of their lifespan are replaced by new cells generated by the adult stem cell pool within the tissue. The rate of renewal is tissue-specific and depends on the rate of stem cell division. Funding Information: We thank members of the laboratory of M.M.M. for helpful discussions and suggestions. The Oncode Institute is partly financed by the Dutch Cancer Society. This work was supported by European Research Council starting grant 242958 (to M.M.M.), EU FP7 grant Marie Curie ITN 608180 'WntsApp' (to M.M.M.), and the Netherlands Organization for Scientific Research (NWO) VICI grant 91815604, ECHO grant 711.013.012, and ZonMW TOP grant 91218050 (to M.M.M.). Publisher Copyright: {\textcopyright} 2019 The Authors",
year = "2020",
month = jan,
day = "1",
doi = "10.1016/j.tcb.2019.10.003",
language = "English",
volume = "30",
pages = "60--73",
journal = "Trends in Cell Biology",
issn = "0962-8924",
publisher = "Elsevier Limited",
number = "1",
}