Virgin Beta Cells Persist throughout Life at a Neogenic Niche within Pancreatic Islets

• Published in: Cell metabolism 2017-04, Vol.25 (4), p.911-926.e6
• Main Authors: van der Meulen, Talitha, Mawla, Alex M., DiGruccio, Michael R., Adams, Michael W., Nies, Vera, Dólleman, Sophie, Liu, Siming, Ackermann, Amanda M., Cáceres, Elena, Hunter, Anna E., Kaestner, Klaus H., Donaldson, Cynthia J., Huising, Mark O.
• Format: Article
• Language: English
• Subjects: Adult; Aging - physiology; alpha cell; beta cell maturation; beta cell neogenesis; Cell Differentiation - genetics; Cell Transdifferentiation; Cellular Microenvironment; diabetes; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - pathology; GCaMP6; Gene Expression Profiling; Glucagon - metabolism; Glucagon-Secreting Cells - metabolism; Glucagon-Secreting Cells - pathology; Humans; insulin; Insulin - metabolism; Insulin-Secreting Cells - cytology; Insulin-Secreting Cells - metabolism; islet architecture; stem cell; Tissue Donors; Transcription, Genetic; transdifferentiation; Urocortin3; Urocortins - metabolism
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2017.03.017

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. [Display omitted] •Virgin β cells that lack Ucn3 form at a neogenic niche at the islet edge•These β cells express insulin, but are functionally and transcriptionally immature•They are an intermediate stage in the transdifferentiation between α and β cells•β cells from α cell origin are functionally indistinguishable from normal β cells Van der Meulen et al. identify a population of immature beta cells originating by transdifferentiation of alpha cells at a pancreatic neogenic niche. Immature beta cells are also present in human islets. They propose targeting this ongoing plasticity within the neogenic niche for beta cell regeneration.