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| Status |
Public on May 04, 2018 |
| Title |
Age-related Islet Inflammation Marks the Proliferative Decline of Pancreatic Beta-cells in Zebrafish |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Individual organisms age at different rates, however, it remains unclear how aging alters the properties of individual cells. Here we show that zebrafish pancreatic beta-cells exhibit heterogeneity in both gene expression and proliferation with age. Individual beta-cells show marked variability in transcripts involved in endoplasmic reticulum stress, inhibition of growth factor signaling and inflammation, including NF-kB signaling. Using a reporter line, we show that NF-kB signaling is indeed activated heterogeneously with age. Notably, beta-cells with higher NF-kB activity proliferate less compared to neighbors with lower activity. Furthermore, NF-kB-signalinghigh beta-cells from younger islets upregulate socs2, a gene naturally expressed in beta-cells from older islets. In turn, socs2 can inhibit proliferation cell-autonomously. NF-kB activation correlates with the recruitment of tnfα-expressing immune cells, pointing towards a role for the islet microenvironment in this activity. We propose that aging is heterogeneous across individual beta-cells and identify NF-kB signaling as a marker of heterogeneity.
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| Overall design |
We used fluorescence-activated cell sorting (FACS) coupled with next generation RNA-Sequencing to profile beta-cells from 3 month post fertilization and 1 year post fertilization animals. total RNA was extracted from FACS sorted beta-cells using Quick-RNA MicroPrep kit (R1050 Zymo Research). Sequencing was performed on llumina HiSeq2500 in 2x75bp paired-end mode. Reads were splice-aligned to the zebrafish genome, GRCz10, using HISAT2. htseq-count was used to assign reads to exons thus eventually getting counts per gene.
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| Contributor(s) |
Janjuha S, Singh SP, Ninov N |
| Citation(s) |
29624168 |
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| Submission date |
Nov 15, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Nikolay Ninov |
| Organization name |
CRTD
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| Lab |
Ninov Lab
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| Street address |
Fetscherstrasse 105
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| City |
Dresden |
| ZIP/Postal code |
01307 |
| Country |
Germany |
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| Platforms (1) |
| GPL18413 |
Illumina HiSeq 2500 (Danio rerio) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA418467 |
| SRA |
SRP125042 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE106938_RAW.tar |
390.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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