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Type: Journal article
Title: ER stress causes rapid loss of intestinal epithelial stemness through activation of the unfolded protein response
Author: Heijmans, J.
van Lidth de Jeude, J.
Koo, B.
Rosekrans, S.
Wielenga, M.
van de Wetering, M.
Ferrante, M.
Lee, A.
Onderwater, J.
Paton, J.
Paton, A.
Mommaas, A.
Kodach, L.
Hardwick, J.
Hommes, D.
Clevers, H.
Muncan, V.
van den Brink, G.
Citation: Cell Reports, 2013; 3(4):1128-1139
Publisher: Elsevier Inc
Issue Date: 2013
ISSN: 2211-1247
Statement of
Jarom 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
Abstract: Stem 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.
Keywords: Intestinal Mucosa
Cells, Cultured
Stem Cells
eIF-2 Kinase
Heat-Shock Proteins
Eukaryotic Initiation Factor-2
RNA, Small Interfering
Signal Transduction
Cell Differentiation
RNA Interference
Unfolded Protein Response
Endoplasmic Reticulum Stress
Endoplasmic Reticulum Chaperone BiP
Rights: Copyright © 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.
DOI: 10.1016/j.celrep.2013.02.031
Appears in Collections:Aurora harvest 4
Molecular and Biomedical Science publications

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