TY - JOUR
T1 - Mex3a Marks a Slowly Dividing Subpopulation of Lgr5+ Intestinal Stem Cells
AU - Barriga, Francisco M.
AU - Montagni, Elisa
AU - Mana, Miyeko
AU - Mendez-Lago, Maria
AU - Hernando-Momblona, Xavier
AU - Sevillano, Marta
AU - Guillaumet-Adkins, Amy
AU - Rodriguez-Esteban, Gustavo
AU - Buczacki, Simon J.A.
AU - Gut, Marta
AU - Heyn, Holger
AU - Winton, Douglas J.
AU - Yilmaz, Omer H.
AU - Attolini, Camille Stephan Otto
AU - Gut, Ivo
AU - Batlle, Eduard
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - 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.
AB - 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.
KW - Lgr5+ ISC heterogeneity
KW - chemotherapy resistance
KW - quiescent stem cell
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U2 - 10.1016/j.stem.2017.02.007
DO - 10.1016/j.stem.2017.02.007
M3 - Article
C2 - 28285904
AN - SCOPUS:85014726810
SN - 1934-5909
VL - 20
SP - 801-816.e7
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 6
ER -