Mex3a Marks a Slowly Dividing Subpopulation of Lgr5+ Intestinal Stem Cells
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Author(s)
Barriga, Francisco M.
Montagni, Elisa
Mendez-Lago, Maria
Hernando-Momblona, Xavier
Sevillano, Marta
Guillaumet-Adkins, Amy
Rodriguez-Esteban, Gustavo
Buczacki, Simon J.A.
Gut, Marta
Heyn, Holger
Date Issued
March 2017
Journal
Cell Stem Cell
Publisher
Elsevier
Citation
Barriga, Francisco M. et al. “Mex3a Marks a Slowly Dividing Subpopulation of Lgr5+ Intestinal Stem Cells.” Cell Stem Cell 20, 6 (June 2017): 801–816 © 2017 Elsevier Inc
Version
Author's final manuscript
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. Lgr5+ intestinal stem cells are considered to be a homogeneous and rapidly proliferating population. Barriga et al. show that the RNA binding protein Mex3a defines a subset of slowly proliferating Lgr5+ cells that contribute to all intestinal lineages with slow kinetics, are resistant to chemotherapy, and support intestinal regeneration. Keywords: Lgr5+ ISC heterogeneity; quiescent stem cell; chemotherapy resistance
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.STEM.2017.02.007
