ER Stress Causes Rapid Loss of Intestinal Epithelial Stemness through Activation of the Unfolded Protein Response
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 dif...
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| Format: | Article |
| Language: | English |
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Elsevier
2013-04-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124713001071 |
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doaj-3c344ff636f84bbcbddc65ce1fcc2e7b2020-11-25T00:23:26ZengElsevierCell Reports2211-12472013-04-01341128113910.1016/j.celrep.2013.02.031ER Stress Causes Rapid Loss of Intestinal Epithelial Stemness through Activation of the Unfolded Protein ResponseJarom Heijmans0Jooske F. van Lidth de Jeude1Bon-Kyoung Koo2Sanne L. Rosekrans3Mattheus C.B. Wielenga4Marc van de Wetering5Marc Ferrante6Amy S. Lee7Jos J.M. Onderwater8James C. Paton9Adrienne W. Paton10A. Mieke Mommaas11Liudmila L. Kodach12James C. Hardwick13Daniël W. Hommes14Hans Clevers15Vanesa Muncan16Gijs R. van den Brink17Tytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, the NetherlandsTytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, the NetherlandsHubrecht Institute, 3584 CT Utrecht, the NetherlandsTytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, the NetherlandsTytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, the NetherlandsHubrecht Institute, 3584 CT Utrecht, the NetherlandsHubrecht Institute, 3584 CT Utrecht, the NetherlandsDepartment of Biochemistry and Molecular Biology, USC/Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USAElectron Microscopy Section, Department of Molecular Cell Biology, Leiden University Medical Center, 2333 ZA Leiden, the NetherlandsResearch Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, South Australia 5005, AustraliaResearch Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, South Australia 5005, AustraliaElectron Microscopy Section, Department of Molecular Cell Biology, Leiden University Medical Center, 2333 ZA Leiden, the NetherlandsDepartment of Gastroenterology and Hepatology, Leiden University Medical Center, 2333 ZA Leiden, the NetherlandsDepartment of Gastroenterology and Hepatology, Leiden University Medical Center, 2333 ZA Leiden, the NetherlandsDepartment of Gastroenterology and Hepatology, Leiden University Medical Center, 2333 ZA Leiden, the NetherlandsHubrecht Institute, 3584 CT Utrecht, the NetherlandsTytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, the NetherlandsTytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands 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. http://www.sciencedirect.com/science/article/pii/S2211124713001071 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 Gijs R. van den Brink |
| spellingShingle |
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 Gijs R. van den Brink ER Stress Causes Rapid Loss of Intestinal Epithelial Stemness through Activation of the Unfolded Protein Response Cell Reports |
| author_facet |
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 Gijs R. van den Brink |
| author_sort |
Jarom Heijmans |
| title |
ER Stress Causes Rapid Loss of Intestinal Epithelial Stemness through Activation of the Unfolded Protein Response |
| title_short |
ER Stress Causes Rapid Loss of Intestinal Epithelial Stemness through Activation of the Unfolded Protein Response |
| title_full |
ER Stress Causes Rapid Loss of Intestinal Epithelial Stemness through Activation of the Unfolded Protein Response |
| title_fullStr |
ER Stress Causes Rapid Loss of Intestinal Epithelial Stemness through Activation of the Unfolded Protein Response |
| title_full_unstemmed |
ER Stress Causes Rapid Loss of Intestinal Epithelial Stemness through Activation of the Unfolded Protein Response |
| title_sort |
er stress causes rapid loss of intestinal epithelial stemness through activation of the unfolded protein response |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2013-04-01 |
| description |
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.
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| url |
http://www.sciencedirect.com/science/article/pii/S2211124713001071 |
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