Mex3a marks a slowly dividing subpopulation of Lgr5+ intestinal stem cells

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 heterog...

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Detalles Bibliográficos
Autores: Barriga de Vicente, Francisco Martín, 1983-, Montagni, Elisa, 1984-, 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., Attolini, Camille Stephan-Otto, Gut, Ivo Glynne, Batlle Gómez, Eduard
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/35344
Acceso en línea:http://hdl.handle.net/10230/35344
http://dx.doi.org/10.1016/j.stem.2017.02.007
Access Level:acceso abierto
Palabra clave:Cèl·lules -- Proliferació
Mucosa intestinal
Proteïnes
Cèl·lules mare
Descripción
Sumario: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.

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