PUBLICATION

Age-related islet inflammation marks the proliferative decline of pancreatic beta-cells in zebrafish

Authors
Janjuha, S., Singh, S.P., Tsakmaki, A., Mousavy-Gharavy, N., Murawala, P., Konantz, J., Birke, S., Hodson, D.J., Rutter, G., Bewick, G., Ninov, N.N.
ID
ZDB-PUB-180407-3
Date
2018
Source
eLIFE   7: (Journal)
Registered Authors
Ninov, Nikolay, Singh, Sumeet Pal
Keywords
cell biology, zebrafish
Datasets
GEO:GSE106938
MeSH Terms
  • Aging*
  • Animals
  • Animals, Genetically Modified
  • Cell Proliferation*
  • Cells, Cultured
  • Gene Expression Profiling
  • Inflammation/immunology
  • Inflammation/metabolism
  • Inflammation/pathology*
  • Inflammation Mediators/metabolism*
  • Insulin-Secreting Cells/immunology
  • Insulin-Secreting Cells/metabolism
  • Insulin-Secreting Cells/pathology*
  • NF-kappa B/genetics
  • NF-kappa B/metabolism*
  • Signal Transduction
  • Single-Cell Analysis
  • Transcriptional Activation
  • Zebrafish/immunology
  • Zebrafish/physiology*
(all 20)
PubMed
29624168 Full text @ Elife
Abstract
The pancreatic islet, a cellular community harboring the insulin-producing beta-cells, is known to undergo age-related alterations. However, only a handful of signals associated with aging have been identified. By comparing beta-cells from younger and older zebrafish, here we show that the aging islets exhibit signs of chronic inflammation. These include recruitment of tnfα-expressing macrophages and the activation of NF-kB signaling in beta-cells. Using a transgenic reporter, we show that NF-kB activity is undetectable in juvenile beta-cells, whereas cells from older fish exhibit heterogeneous NF-kB activity. We link this heterogeneity to differences in gene expression and proliferation. Beta-cells with high NF-kB signaling proliferate significantly less compared to their neighbors with low activity. The NF-kB signalinghi cells also exhibit premature upregulation of socs2, an age-related gene that inhibits beta-cell proliferation. Together, our results show that NF-kB activity marks the asynchronous decline in beta-cell proliferation with advancing age.
Genes / Markers
Marker Marker Type Name
actb1GENEactin, beta 1
bmi1bGENEbmi1 polycomb ring finger oncogene 1b
cdt1GENEchromatin licensing and DNA replication factor 1
cishaGENEcytokine inducible SH2-containing protein a
eef1a1l1GENEeukaryotic translation elongation factor 1 alpha 1, like 1
gmnnGENEgeminin DNA replication inhibitor
insGENEpreproinsulin
isl1aGENEISL LIM homeobox 1a
neurod1GENEneuronal differentiation 1
nfkbiaaGENEnuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha a
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Figures
Figure Gallery (12 images) / 2
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
gl23TgTransgenic Insertion
    nc1TgTransgenic Insertion
      pd1028TgTransgenic Insertion
        s892TgTransgenic Insertion
          s934TgTransgenic Insertion
            s946TgTransgenic Insertion
              s948TgTransgenic Insertion
                tud202TgTransgenic Insertion
                  tud203TgTransgenic Insertion
                    1 - 9 of 9
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                    Human Disease / Model
                    No data available
                    Sequence Targeting Reagents
                    No data available
                    Fish
                    No data available
                    Antibodies
                    Orthology
                    No data available
                    Engineered Foreign Genes
                    Marker Marker Type Name
                    CeruleanEFGCerulean
                    CFPEFGCFP
                    EGFPEFGEGFP
                    GCaMPEFGGCaMP
                    GFPEFGGFP
                    LuciferaseEFGLuciferase
                    mAGFPEFGmAGFP
                    mCherryEFGmCherry
                    mKOFP2EFGmKOFP2
                    NTREFGNTR
                    1 - 10 of 11
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                    Mapping
                    No data available
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                    Citation
                    Janjuha, S., Singh, S.P., Tsakmaki, A., Mousavy-Gharavy, N., Murawala, P., Konantz, J., Birke, S., Hodson, D.J., Rutter, G., Bewick, G., Ninov, N.N. (2018) Age-related islet inflammation marks the proliferative decline of pancreatic beta-cells in zebrafish. eLIFE. 7.