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|Title:||Mex3a Marks a Slowly Dividing Subpopulation of Lgr5+ Intestinal Stem Cells|
|Author:||Barriga, Francisco M.|
Méndez Lago, María
Hernando Momblona, Xavier
Guillaumet Adkins, Amy
Rodríguez Esteban, Gustavo
Buczacki, Simon J. A.
Winton, Douglas J.
Yilmaz, Omer H.
Stephan-Otto Attolini, Camille
|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: http://dx.doi.org/10.1016/j.stem.2017.02.007|
|It is part of:||Cell Stem Cell, 2017|
|Appears in Collections:||Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))|
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