Barriga, Francisco M.Montagni, ElisaMana, MiyekoMéndez Lago, MaríaHernando Momblona, XavierSevillano, MartaGuillaumet Adkins, AmyRodríguez Esteban, GustavoBuczacki, Simon J. A.Gut, MartaHeyn, HolgerWinton, Douglas J.Yilmaz, Omer H.Stephan-Otto Attolini, CamilleGut, Ivo G.Batlle, Eduard2017-07-132018-03-092017-03-091934-5909https://hdl.handle.net/2445/113724Highly 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.62 p.application/pdfapplication/pdfengcc by-nc-nd (c) Elsevier, 2017http://creativecommons.org/licenses/by-nc-nd/3.0/es/Cèl·lules mareRNAStem cellsRNAinfo:eu-repo/semantics/article2017-07-13info:eu-repo/semantics/openAccess