title: Robust intestinal homeostasis relies on cellular plasticity in enteroblasts mediated by miR-8-Escargot switch.
abstract: The intestinal epithelium is remarkably robust despite perturbations and demand uncertainty. Here, we investigate the basis of such robustness using novel tracing methods that allow simultaneously capturing the dynamics of stem and committed progenitor cells (called enteroblasts) and intestinal cell turnover with spatiotemporal resolution. We found that intestinal stem cells (ISCs) divide "ahead" of demand during Drosophila midgut homeostasis. Their newborn enteroblasts, on the other hand, take on a highly polarized shape, acquire invasive properties and motility. They extend long membrane protrusions that make cell-cell contact with mature cells, while exercising a capacity to delay their final differentiation until a local demand materializes. This cellular plasticity is mechanistically linked to the epithelial-mesenchymal transition (EMT) programme mediated by escargot, a snail family gene. Activation of the conserved microRNA miR-8/miR-200 in "pausing" enteroblasts in response to a local cell loss promotes timely terminal differentiation via a reverse MET by antagonizing escargot. Our findings unveil that robust intestinal renewal relies on hitherto unrecognized plasticity in enteroblasts and reveal their active role in sensing and/or responding to local demand.
authors.affiliation: Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Miguel Hernández (UMH), Sant Joan, Alicante, Spain.
authors.forename: Zeus A
authors.initials: ZA
authors.lastname: Antonello
authors.affiliation: Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Miguel Hernández (UMH), Sant Joan, Alicante, Spain.
authors.forename: Tobias
authors.initials: T
authors.lastname: Reiff
authors.affiliation: Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Miguel Hernández (UMH), Sant Joan, Alicante, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Ballesta-Illan
authors.affiliation: Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Miguel Hernández (UMH), Sant Joan, Alicante, Spain m.dominguez@umh.es.
authors.forename: Maria
authors.initials: M
authors.lastname: Dominguez
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D003433:Crosses, Genetic; D017931:DNA Primers / Q000235:genetics; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology / Q000502:physiology*; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013234:Stem Cells / Q000502:physiology*; D059008:Time-Lapse Imaging
chemical_list: D017931:DNA Primers; D029721:Drosophila Proteins; D035683:MicroRNAs; C467520:esg protein, Drosophila; C526630:MIRN8 microRNA, Drosophila
keywords: EMT/MET; Escargot/Snail2–miR‐8/miR‐200; intestinal homeostasis; intestinal renewal; stemness