PUBLICATION

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

Authors
Singh, S.P., Janjuha, S., Hartmann, T., Kayisoglu, Ö., Konantz, J., Birke, S., Murawala, P., Alfar, E.A., Murata, K., Eugster, A., Tsuji, N., Morrissey, E.R., Brand, M., Ninov, N.
ID
ZDB-PUB-170924-5
Date
2017
Source
Nature communications   8: 664 (Journal)
Registered Authors
Brand, Michael, Kayisoglu, Ozge, Ninov, Nikolay, Singh, Sumeet Pal
Keywords
Differentiation, Pancreas, Zebrafish
MeSH Terms
  • Urocortins/metabolism
  • Cell Proliferation
  • Cell Lineage
  • Insulin-Secreting Cells/cytology*
  • Insulin-Secreting Cells/drug effects
  • Insulin-Secreting Cells/physiology
  • Tamoxifen/analogs & derivatives
  • Tamoxifen/pharmacology
  • Cytological Techniques/methods
  • Animals, Genetically Modified
  • Animals
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Islets of Langerhans/cytology*
  • Islets of Langerhans/embryology
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/drug effects
  • Glucose/metabolism
(all 18)
PubMed
28939870 Full text @ Nat. Commun.
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.Βeta-cells have recently been shown to be heterogeneous with regard to morphology and function. Here, the authors show that β-cells in zebrafish switch from proliferative to functional states with increasing time since β-cell birth, leading to functional and proliferative heterogeneity.
Genes / Markers
Figures
Figure Gallery (22 images) / 3
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
cz1701TgTransgenic Insertion
    gz19TgTransgenic Insertion
      s821TgTransgenic Insertion
        s892TgTransgenic Insertion
          s934TgTransgenic Insertion
            s939TgTransgenic Insertion
              s940TgTransgenic Insertion
                s946TgTransgenic Insertion
                  s948TgTransgenic Insertion
                    s951
                      		Insertion
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      No data available
                      Fish
                      Fish
                      WT
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                      Antibodies
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      CeruleanEFGCerulean
                      CFPEFGCFP
                      CreEFGCre
                      DsRedEFGDsRed
                      EGFPEFGEGFP
                      EYFPEFGEYFP
                      GAL4EFGGAL4
                      GCaMPEFGGCaMP
                      GFPEFGGFP
                      LuciferaseEFGLuciferase
                      1 - 10 of 18
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                      Mapping
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                      Citation
                      Singh, S.P., Janjuha, S., Hartmann, T., Kayisoglu, Ö., Konantz, J., Birke, S., Murawala, P., Alfar, E.A., Murata, K., Eugster, A., Tsuji, N., Morrissey, E.R., Brand, M., Ninov, N. (2017) Different developmental histories of beta-cells generate functional and proliferative heterogeneity during islet growth. Nature communications. 8:664.