Different developmental histories of beta-cells generate functional and proliferative heterogeneity during islet growth

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Sumeet Pal Singh - , Pancreatic beta-cell Biology and Regeneration (NFoG), Deutsche Forschungsgemeinschaft (DFG), Center for Regenerative Therapies Dresden (CRTD) (Autor:in)
  • Sharan Janjuha - , Deutsche Forschungsgemeinschaft (DFG), Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Technische Universität Dresden (Autor:in)
  • Theresa Hartmann - , Deutsche Forschungsgemeinschaft (DFG) (Autor:in)
  • Ozge Kayisoglu - , Deutsche Forschungsgemeinschaft (DFG) (Autor:in)
  • Judith Konantz - , Core Facility Fischhaltung, Deutsche Forschungsgemeinschaft (DFG), Center for Regenerative Therapies Dresden (CRTD) (Autor:in)
  • Sarah Birke - , Deutsche Forschungsgemeinschaft (DFG) (Autor:in)
  • Priyanka Murawala - , Deutsche Forschungsgemeinschaft (DFG), Center for Regenerative Therapies Dresden (CRTD) (Autor:in)
  • Ezzaldin Ahmed Alfar - , Institut für Pharmakologie und Toxikologie, Deutsche Forschungsgemeinschaft (DFG), Center for Regenerative Therapies Dresden (CRTD) (Autor:in)
  • Kei Murata - , Professur für Molekulare Entwicklungsgenetik, Deutsche Forschungsgemeinschaft (DFG), Center for Regenerative Therapies Dresden (CRTD) (Autor:in)
  • Anne Eugster - , Deutsche Forschungsgemeinschaft (DFG) (Autor:in)
  • Naoki Tsuji - , Daiichi Sankyo Company, Limited (Autor:in)
  • Edward R. Morrissey - , University of Oxford (Autor:in)
  • Michael Brand - , Professur für Molekulare Entwicklungsgenetik, Deutsche Forschungsgemeinschaft (DFG), Center for Regenerative Therapies Dresden (CRTD) (Autor:in)
  • Nikolay Ninov - , Professur für Zellbiologie und Regeneration von Betazellen, Deutsche Forschungsgemeinschaft (DFG), Center for Regenerative Therapies Dresden (CRTD), Paul Langerhans Institut Dresden (PLID) des Helmholtz Zentrum München, Technische Universität Dresden, Universitätsklinikum Carl Gustav Carus Dresden, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) - Standort Dresden (Autor:in)

Abstract

The proliferative and functional heterogeneity among seemingly uniform cells is a universal phenomenon. Identifying the underlying factors requires single-cell analysis of function and proliferation. Here we show that the pancreatic beta-cells in zebrafish exhibit different growth-promoting and functional properties, which in part reflect differences in the time elapsed since birth of the cells. Calcium imaging shows that the beta-cells in the embryonic islet become functional during early zebrafish development. At later stages, younger beta-cells join the islet following differentiation from post-embryonic progenitors. Notably, the older and younger beta-cells occupy different regions within the islet, which generates topological asymmetries in glucose responsiveness and proliferation. Specifically, the older beta-cells exhibit robust glucose responsiveness, whereas younger beta-cells are more proliferative but less functional. As the islet approaches its mature state, heterogeneity diminishes and beta-cells synchronize function and proliferation. Our work illustrates a dynamic model of heterogeneity based on evolving proliferative and functional beta-cell states.

Details

OriginalspracheEnglisch
Seitenumfang16
FachzeitschriftNature communications
Jahrgang8
PublikationsstatusVeröffentlicht - 22 Sept. 2017
Peer-Review-StatusJa

Externe IDs

PubMed 28939870
Scopus 85028705417

Schlagworte

Schlagwörter

  • Alpha cell, Characteristic features, Fluorescent proteins, Pancreas development, Expressing cells, Zebrafish, Mouse, Maturation, Reveals, Adult