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Title: Mex3a Marks a Slowly Dividing Subpopulation of Lgr5+ Intestinal Stem Cells
Author: 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
Keywords: Cèl·lules mare
Stem cells
Issue Date: 9-Mar-2017
Publisher: Elsevier
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.
Note: Versió postprint del document publicat a:
It is part of: Cell Stem Cell, 2017
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ISSN: 1934-5909
Appears in Collections:Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

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