Molecular Profiling of NOD mice reveals a novel regulator of insulitin onset
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ABSTRACT: Non-obese Diabetes (NOD) mice are an established spontaneous model for Type 1 Diabetes (T1D), emulating diabetes development through insulitis. Using next generation sequencing, coupled with pathways analysis, the molecular fingerprint of early insulitis was mapped in a cohort of mice ranging from four to 12 weeks of age. The resulted dynamic timeline revealed an initial decrease in proliferative capacity followed by the emergence of an inflammatory signature between 6- and 8-weeks, that increases to a regulatory plateau between 10- and 12-weeks. The inflammatory signature is identified by activation of central immunogenic factors such as Infg, Il1b, Tnfa, and activation of canonical inflammatory signalling. Prodding of the regulatory landscape identified the transcription factor Atf3 as a potential novel regulator of inflammatory signalling in the NOD Islet. Furthermore, the Hedgehog (Hh) signaling pathway correlated with Atf3 regulation, hinting at role for the two in regulating the inflamed islet, however, further studies are needed to establish the nature of this connection.
ORGANISM(S): Mus musculus
PROVIDER: GSE256150 | GEO | 2024/07/03
REPOSITORIES: GEO
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