Lorenzo, Petra IFuente-Martín, EstherBrun, ThierryCobo-Vuilleumier, NadiaJimenez-Moreno, Carmen MaríaG Herrera Gomez, IreneLópez Noriega, LiviaMellado-Gil, José ManuelMartin-Montalvo, AlejandroSoria, BernatGauthier, Benoit R2016-07-042016-07-042015Lorenzo PI, Fuente-Martín E, Brun T, Cobo-Vuilleumier N, Jimenez-Moreno CM, G Herrera Gomez I, et al. PAX4 Defines an Expandable β-Cell Subpopulation in the Adult Pancreatic Islet. Sci Rep; 5:15672http://hdl.handle.net/10668/2249Journal Article; Research Support, Non-U.S. Gov't;PAX4 is a key regulator of pancreatic islet development whilst in adult acute overexpression protects β-cells against stress-induced apoptosis and stimulates proliferation. Nonetheless, sustained PAX4 expression promotes β-cell dedifferentiation and hyperglycemia, mimicking β-cell failure in diabetic patients. Herein, we study mechanisms that allow stringent PAX4 regulation endowing favorable β-cell adaptation in response to changing environment without loss of identity. To this end, PAX4 expression was monitored using a mouse bearing the enhanced green fluorescent protein (GFP) and cre recombinase construct under the control of the islet specific pax4 promoter. GFP was detected in 30% of islet cells predominantly composed of PAX4-enriched β-cells that responded to glucose-induced insulin secretion. Lineage tracing demonstrated that all islet cells were derived from PAX4(+) progenitor cells but that GFP expression was confined to a subpopulation at birth which declined with age correlating with reduced replication. However, this GFP(+) subpopulation expanded during pregnancy, a state of active β-cell replication. Accordingly, enhanced proliferation was exclusively detected in GFP(+) cells consistent with cell cycle genes being stimulated in PAX4-overexpressing islets. Under stress conditions, GFP(+) cells were more resistant to apoptosis than their GFP(-) counterparts. Our data suggest PAX4 defines an expandable β-cell sub population within adult islets.enCell growthndocrine system and metabolic diseasesAumento de la célulaEnfermedades metabólicasEnfermedades del sistema endocrinoMedical Subject Headings::Anatomy::Digestive System::Pancreas::Islets of LangerhansMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::ApoptosisMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell DedifferentiationMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Luminescent Proteins::Green Fluorescent ProteinsMedical Subject Headings::Anatomy::Cells::Endocrine Cells::Enteroendocrine Cells::Insulin-Secreting CellsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Peptide Hormones::Pancreatic Hormones::InsulinsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Miceresearch article26503027open access10.1038/srep156722045-2322PMC4622080