Mex3a marks a slowly dividing subpopulation of Lgr5+ intestinal stem cells

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  • dc.contributor.author Barriga de Vicente, Francisco Martín, 1983-ca
  • dc.contributor.author Montagni, Elisa, 1984-ca
  • dc.contributor.author Mana, Miyekoca
  • dc.contributor.author Méndez Lago, Maríaca
  • dc.contributor.author Hernando-Momblona, Xavierca
  • dc.contributor.author Sevillano, Martaca
  • dc.contributor.author Guillaumet-Adkins, Amyca
  • dc.contributor.author Rodríguez Esteban, Gustavoca
  • dc.contributor.author Buczacki, Simon J.A.ca
  • dc.contributor.author Gut, Martaca
  • dc.contributor.author Heyn, Holgerca
  • dc.contributor.author Winton, Douglas J.ca
  • dc.contributor.author Yilmaz, Omer H.ca
  • dc.contributor.author Attolini, Camille Stephan-Ottoca
  • dc.contributor.author Gut, Ivo Glynneca
  • dc.contributor.author Batlle Gómez, Eduardca
  • dc.date.accessioned 2018-08-21T06:18:24Z
  • dc.date.available 2018-08-21T06:18:24Z
  • dc.date.issued 2017
  • dc.description.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.
  • dc.description.sponsorship This work has been financed by the European Research Council (ERC advanced grant 340176) and the Spanish Ministry of Science and Competitivity (SAF2011-27068)
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Barriga FM, Montagni E, Mana M, Mendez-Lago M, Hernando-Momblona X, Sevillano M et al. Mex3a marks a slowly dividing subpopulation of Lgr5+ intestinal stem cells. Cell Stem Cell. 2017 June;20(6):801-16. DOI: 10.1016/j.stem.2017.02.007
  • dc.identifier.doi http://dx.doi.org/10.1016/j.stem.2017.02.007
  • dc.identifier.issn 1934-5909
  • dc.identifier.uri http://hdl.handle.net/10230/35344
  • dc.language.iso eng
  • dc.publisher Elsevierca
  • dc.relation.ispartof Cell Stem Cell. 2017 June;20(6):801-16
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/340176
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011-27068
  • dc.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
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.subject.other Cèl·lules -- Proliferació
  • dc.subject.other Mucosa intestinal
  • dc.subject.other Proteïnes
  • dc.subject.other Cèl·lules mare
  • dc.title Mex3a marks a slowly dividing subpopulation of Lgr5+ intestinal stem cellsca
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion