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Title: | Mex3a marks a slowly dividing subpopulation of Lgr5+ intestinal stem cells |
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Author: | Barriga de Vicente, Francisco Martín, 1983-; Montagni, Elisa, 1984-; Mana, Miyeko; Méndez Lago, María; Hernando-Momblona, Xavier; Sevillano, Marta; Guillaumet-Adkins, Amy; Rodríguez Esteban, Gustavo; Buczacki, Simon J.A.; Gut, Marta; Heyn, Holger; Winton, Douglas J.; Yilmaz, Omer H.; Attolini, Camille Stephan-Otto; Gut, Ivo Glynne; Batlle Gómez, Eduard |
Abstract: | Highly proliferative Lgr5+ stem cells maintain the intestinal epithelium and are thought to be largely homogeneous. Although quiescent intestinal stem cell (ISC) populations have been described, the identity and features of such a population remain controversial. Here we report unanticipated heterogeneity within the Lgr5+ ISC pool. We found that expression of the RNA-binding protein Mex3a labels a slowly cycling subpopulation of Lgr5+ ISCs that contribute to all intestinal lineages with distinct kinetics. Single-cell transcriptome profiling revealed that Lgr5+ cells adopt two discrete states, one of which is defined by a Mex3a expression program and relatively low levels of proliferation genes. During homeostasis, Mex3a+ cells continually shift into the rapidly dividing, self-renewing ISC pool. Chemotherapy and radiation preferentially target rapidly dividing Lgr5+ cells but spare the Mex3a-high/Lgr5+ population, helping to promote regeneration of the intestinal epithelium following toxic insults. Thus, Mex3a defines a reserve-like ISC population within the Lgr5+ compartment. |
Abstract: | This work has been financed by the European Research Council (ERC advanced grant 340176) and the Spanish Ministry of Science and Competitivity (SAF2011-27068) |
Subject(s): | -Cèl·lules -- Proliferació -Mucosa intestinal -Proteïnes -Cèl·lules mare |
Rights: | © Elsevier This is the published version of an article http://dx.doi.org/10.1016/j.stem.2017.02.007 that appeared in the journal Cell Stem Cell. It is published in an Open Archive under an Elsevier user license. Details of this licence are available here: https://www.elsevier.com/about/our-business/policies/open-access-licenses/elsevier-user-license |
Document type: | Article Article - Published version |
Published by: | Elsevier |
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