ER Stress Causes Rapid Loss of Intestinal Epithelial Stemness through Activation of the Unfolded Protein Response

• DOI: 10.1016/j.celrep.2013.02.031
• Publication Date: 2013-03-28T20:19:29Z
• Authors: Jarom Heijmans; Jooske F. van Lid...; Bon-Kyoung Koo; Sanne L. Rosekrans; Mattheus C.B. Wie...; 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 B...
• Keywords: Intestinal epithelium; Organoid; Intestinal mucosa

Stem cells generate rapidly dividing transit-amplifying that have lost the capacity for self-renewal but cycle a number of times until they exit cell and undergo terminal differentiation. We know very little type signals trigger earliest steps stem differentiation mediate to transition. show in normal intestinal epithelium, endoplasmic reticulum (ER) stress activity unfolded protein response (UPR) are induced at transition from cell. Induction ER causes loss stemness Perk-eIF2α-dependent manner. Inhibition Perk-eIF2α signaling results accumulation organoid culture primary epithelium. Our findings UPR plays an important role regulation epithelial