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...

Descripción completa

Detalles Bibliográficos
Autores: 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 G., Batlle, Eduard
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
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:2445/113724
Acceso en línea:https://hdl.handle.net/2445/113724
Access Level:acceso abierto
Palabra clave:Cèl·lules mare
RNA
Stem cells
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.

Similares en LA Referencia