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ER stress causes rapid loss of intestinal epithelial stemness through activation of the unfolded protein response

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dc.contributor.authorHeijmans, J.
dc.contributor.authorvan Lidth de Jeude, J.
dc.contributor.authorKoo, B.
dc.contributor.authorRosekrans, S.
dc.contributor.authorWielenga, M.
dc.contributor.authorvan de Wetering, M.
dc.contributor.authorFerrante, M.
dc.contributor.authorLee, A.
dc.contributor.authorOnderwater, J.
dc.contributor.authorPaton, J.
dc.contributor.authorPaton, A.
dc.contributor.authorMommaas, A.
dc.contributor.authorKodach, L.
dc.contributor.authorHardwick, J.
dc.contributor.authorHommes, D.
dc.contributor.authorClevers, H.
dc.contributor.authorMuncan, V.
dc.contributor.authorvan den Brink, G.
dc.date.issued2013
dc.description.abstractStem cells generate rapidly dividing transit-amplifying cells that have lost the capacity for self-renewal but cycle for a number of times until they exit the cell cycle and undergo terminal differentiation. We know very little of the type of signals that trigger the earliest steps of stem cell differentiation and mediate a stem cell to transit-amplifying cell transition. We show that in normal intestinal epithelium, endoplasmic reticulum (ER) stress and activity of the unfolded protein response (UPR) are induced at the transition from stem cell to transit-amplifying cell. Induction of ER stress causes loss of stemness in a Perk-eIF2α-dependent manner. Inhibition of Perk-eIF2α signaling results in stem cell accumulation in organoid culture of primary intestinal epithelium. Our findings show that the UPR plays an important role in the regulation of intestinal epithelial stem cell differentiation.
dc.description.statementofresponsibilityJarom Heijmans, Jooske F. van Lidth de Jeude, Bon-Kyoung Koo, Sanne L. Rosekrans, Mattheus C.B. Wielenga, Marc van de Wetering, Marc Ferrante, Amy S. Lee, Jos J.M. Onderwater, James C. Paton, Adrienne W. Paton, A. Mieke Mommaas, Liudmila L. Kodach, James C. Hardwick, Daniël W. Hommes, Hans Clevers, Vanesa Muncan, and Gijs R. van den Brink
dc.identifier.citationCell Reports, 2013; 3(4):1128-1139
dc.identifier.doi10.1016/j.celrep.2013.02.031
dc.identifier.issn2211-1247
dc.identifier.issn2211-1247
dc.identifier.orcidPaton, J. [0000-0001-9807-5278]
dc.identifier.urihttp://hdl.handle.net/2440/78990
dc.language.isoen
dc.publisherElsevier Inc
dc.rightsCopyright © 2013 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.source.urihttps://doi.org/10.1016/j.celrep.2013.02.031
dc.subjectIntestinal Mucosa
dc.subjectCells, Cultured
dc.subjectStem Cells
dc.subjectAnimals
dc.subjectMice
dc.subjecteIF-2 Kinase
dc.subjectHeat-Shock Proteins
dc.subjectEukaryotic Initiation Factor-2
dc.subjectRNA, Small Interfering
dc.subjectSignal Transduction
dc.subjectCell Differentiation
dc.subjectRNA Interference
dc.subjectMutation
dc.subjectUnfolded Protein Response
dc.subjectEndoplasmic Reticulum Stress
dc.subjectEndoplasmic Reticulum Chaperone BiP
dc.titleER stress causes rapid loss of intestinal epithelial stemness through activation of the unfolded protein response
dc.typeJournal article
pubs.publication-statusPublished

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