Aldehyde dehydrogenase activity is necessary for beta cell development and functionality in mice
Transcriptomics Dataset
FAIR Metrics
0 evaluations
General Information
| Accession | GSE58025 |
| Title | Aldehyde dehydrogenase activity is necessary for beta cell development and functionality in mice |
| Description | Aims/hypothesis Pancreatic beta cells maintain glucose homeostasis and beta cell dysfunction is a major risk factor in developing diabetes. Therefore, understanding the developmental regulatory networks that define a fully functional beta cell is important for elucidating the genetic origins of the disease. Aldehyde dehydrogenase activity has been associated with stem/progenitor cells and we have previously shown that Aldh1b1 is specifically expressed in pancreas progenitor pools. Here we address the hypothesis that Aldh1b1 may regulate the timing of the appearance and eventual functionality of beta cells. Methods We generated an Aldh1b1-knockout mouse line (Aldh1b1tm1lacZ) and used this to study pancreatic development, beta cell functionality and glucose homeostasis in the absence of Aldh1b1 function. Results Differentiation in the developing pancreas of Aldh1b1tm1lacZ null mice was accelerated. Transcriptome analyses of newborn and adult islets showed misregulation of key beta cell transcription factors and genes crucial for beta cell function. Functional analyses showed that glucose-stimulated insulin secretion was severely compromised in islets isolated from null mice. Several key features of beta cell functionality were affected, including control of oxidative stress, glucose sensing, stimulus-coupling secretion and secretory granule biogenesis. As a result of beta cell dysfunction, homozygous mice developed glucose intolerance and age-dependent hyperglycaemia. Conclusions/interpretation These findings show that Aldh1b1 influences the timing of the transition from the pancreas endocrine progenitor to the committed beta cell and demonstrate that changes in the timing of this transition lead to beta cell dysfunction and thus constitute a diabetes risk factor later in life. |
| Landing Page | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE58025 |
| Repository | Gene Expression Omnibus |
Related Datasets
GSE59622
Genes regulated by the winged helix transcription factor Rfx6 in adult beta cell in the mouse
1
GSE78966
Progenitor Cell Marker Aldehyde Dehydrogenase 1a3 Defines a Subset of Failing Pancreatic Beta Cells in Diabetic Mice
1
Tools
used to analyze the dataset
Canned Analyses
generated with the dataset
FAIR Evaluation
Sorry, you must be signed in to evaluate this object.
