{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wong VW"],"funding":["Cancer Research UK","Medical Research Council","Wellcome Trust"],"pagination":["401-8"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3378643"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(4)"],"pubmed_abstract":["Maintenance of adult tissues is carried out by stem cells and is sustained throughout life in a highly ordered manner. Homeostasis within the stem-cell compartment is governed by positive- and negative-feedback regulation of instructive extrinsic and intrinsic signals. ErbB signalling is a prerequisite for maintenance of the intestinal epithelium following injury and tumour formation. As ErbB-family ligands and receptors are highly expressed within the stem-cell niche, we hypothesize that strong endogenous regulators must control the pathway in the stem-cell compartment. Here we show that Lrig1, a negative-feedback regulator of the ErbB receptor family, is highly expressed by intestinal stem cells and controls the size of the intestinal stem-cell niche by regulating the amplitude of growth-factor signalling. Intestinal stem-cell maintenance has so far been attributed to a combination of Wnt and Notch activation and Bmpr inhibition. Our findings reveal ErbB activation as a strong inductive signal for stem-cell proliferation. This has implications for our understanding of ErbB signalling in tissue development and maintenance and the progression of malignant disease."],"journal":["Nature cell biology"],"pubmed_title":["Lrig1 controls intestinal stem-cell homeostasis by negative regulation of ErbB signalling."],"pmcid":["PMC3378643"],"funding_grant_id":["17044","G0800784B","088454","979886","G0800784","079249"],"pubmed_authors":["Wabik A","Watt FM","Winton DJ","Jensen KB","Itami S","Wright NA","Clevers H","Buczacki S","Trotter MW","Wong VW","Stange DE","Page ME","van de Wetering M","Poulsom R"],"additional_accession":[]},"is_claimable":false,"name":"Lrig1 controls intestinal stem-cell homeostasis by negative regulation of ErbB signalling.","description":"Maintenance of adult tissues is carried out by stem cells and is sustained throughout life in a highly ordered manner. Homeostasis within the stem-cell compartment is governed by positive- and negative-feedback regulation of instructive extrinsic and intrinsic signals. ErbB signalling is a prerequisite for maintenance of the intestinal epithelium following injury and tumour formation. As ErbB-family ligands and receptors are highly expressed within the stem-cell niche, we hypothesize that strong endogenous regulators must control the pathway in the stem-cell compartment. Here we show that Lrig1, a negative-feedback regulator of the ErbB receptor family, is highly expressed by intestinal stem cells and controls the size of the intestinal stem-cell niche by regulating the amplitude of growth-factor signalling. Intestinal stem-cell maintenance has so far been attributed to a combination of Wnt and Notch activation and Bmpr inhibition. Our findings reveal ErbB activation as a strong inductive signal for stem-cell proliferation. This has implications for our understanding of ErbB signalling in tissue development and maintenance and the progression of malignant disease.","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Mar","modification":"2021-02-20T04:19:07Z","creation":"2019-03-27T00:54:45Z"},"accession":"S-EPMC3378643","cross_references":{"pubmed":["22388892"],"doi":["10.1038/ncb2464"]}}