title: Virgin Beta Cells Persist throughout Life at a Neogenic Niche within Pancreatic Islets.
abstract: Postnatal maintenance or regeneration of pancreatic beta cells is considered to occur exclusively via the replication of existing beta cells, but clinically meaningful restoration of human beta cell mass by proliferation has never been achieved. We discovered a population of immature beta cells that is present throughout life and forms from non-beta precursors at a specialized micro-environment or "neogenic niche" at the islet periphery. These cells express insulin, but lack other key beta cell markers, and are transcriptionally immature, incapable of sensing glucose, and unable to support calcium influx. They constitute an intermediate stage in the transdifferentiation of alpha cells to cells that are functionally indistinguishable from conventional beta cells. We thus identified a lifelong source of new beta cells at a specialized site within healthy islets. By comparing co-existing immature and mature beta cells within healthy islets, we stand to learn how to mature insulin-expressing cells into functional beta cells.
authors.affiliation: Department of Neurobiology, Physiology, and Behavior, College of Biological Sciences, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Talitha
authors.initials: T
authors.lastname: van der Meulen
authors.affiliation: Department of Neurobiology, Physiology, and Behavior, College of Biological Sciences, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Alex M
authors.initials: AM
authors.lastname: Mawla
authors.affiliation: Department of Neurobiology, Physiology, and Behavior, College of Biological Sciences, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: DiGruccio
authors.affiliation: Waitt Advanced Biophotonics Center, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Adams
authors.affiliation: Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Vera
authors.initials: V
authors.lastname: Nies
authors.affiliation: Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Sophie
authors.initials: S
authors.lastname: Dólleman
authors.affiliation: Department of Neurobiology, Physiology, and Behavior, College of Biological Sciences, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Siming
authors.initials: S
authors.lastname: Liu
authors.affiliation: Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Ackermann
authors.affiliation: Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Cáceres
authors.affiliation: Department of Neurobiology, Physiology, and Behavior, College of Biological Sciences, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Hunter
authors.affiliation: Department of Genetics and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Kaestner
authors.affiliation: Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: Donaldson
authors.affiliation: Department of Neurobiology, Physiology, and Behavior, College of Biological Sciences, University of California, Davis, Davis, CA 95616, USA; Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, Davis, CA 95616, USA. Electronic address: mhuising@ucdavis.edu.
authors.forename: Mark O
authors.initials: MO
authors.lastname: Huising
mesh_terms: D000328:Adult; D000375:Aging / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics; D054338:Cell Transdifferentiation; D060833:Cellular Microenvironment; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D005934:Glucagon / Q000378:metabolism; D050416:Glucagon-Secreting Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D014019:Tissue Donors; D014158:Transcription, Genetic; D054832:Urocortins / Q000378:metabolism
chemical_list: D007328:Insulin; C000602668:Ucn3 protein, mouse; D054832:Urocortins; D005934:Glucagon
keywords: GCaMP6; Urocortin3; alpha cell; beta cell maturation; beta cell neogenesis; diabetes; insulin; islet architecture; stem cell; transdifferentiation