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Mex3a Marks a Slowly Dividing Subpopulation of Lgr5+ Intestinal Stem Cells
Barriga, Francisco M.; Montagni, Elisa; 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.; Stephan-Otto Attolini, Camille; Gut, Ivo; Batlle, Eduard
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.
Cèl·lules mare
RNA
Stem cells
RNA
cc by-nc-nd (c) Elsevier, 2017
info:eu-repo/semantics/embargoedAccess
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
Artículo
info:eu-repo/semantics/acceptedVersion
Elsevier
         

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