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| Status |
Public on Jul 12, 2023 |
| Title |
Beta cell dysfunction and dedifferentiation induced by Bone Morphogenetic Protein (BMP)-2 is associated with histone modifications and decreased NeuroD1 chromatin binding {RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Insufficient insulin secretion is a hallmark of type 2 diabetes and has been attributed to beta cell identity loss characterized by decreased expression of several key beta cell genes. The pro-inflammatory factor BMP-2 is upregulated in islets of Langerhans from diabetic individuals and acts as an inhibitor of beta cell function and proliferation. Exposure to BMP-2 induces expression of Id1-4, Hes-1 and Hey-1, transcriptional regulators associated with loss of differentiation. The aim of this study was to investigate the mechanism of BMP-2 induced beta cell dysfunction and maturity. Mouse islets exposed to BMP-2 for 10 days showed impaired insulin secretion and beta cell proliferation. BMP-2-induced beta cell dysfunction was associated with decreased expression of beta cell specific identity and proliferation markers such as Ins1, Ucn3 and Ki67 but increased expression of Id1-4, Hes-1 and Hey-1. Top 30 most regulated proteins significantly correlated with corresponding mRNA expression. BMP-2 induced gene expression changes were associated with a predominant reduction in acetylation of H3K27 and a decrease in NeuroD1 chromatin binding activity. These results show that BMP-2-induced beta cell dysfunction is associated with epigenetic changes, predominantly a reduction in H3K27ac and a decrease in NeuroD1 DNA binding resulting in altered beta cell gene expression.
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| Overall design |
RNA-seq of pancreatic islets were cultured in the absence or presence of 50ng/ml BMP2
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| Contributor(s) |
Urizar AI, Prause M, Ingerslev LR, Wortham M, Sui Y, Sander M, Williams K, Barrès R, Larsen MR, Christensen GL, Billestrup N |
| Citation(s) |
37407581 |
| |
| Submission date |
Oct 20, 2022 |
| Last update date |
Jul 13, 2023 |
| Contact name |
Matthew Wortham |
| E-mail(s) |
mwortham@ucsd.edu
|
| Phone |
8582460588
|
| Organization name |
University of California, San Diego
|
| Lab |
Maike Sander
|
| Street address |
2880 Torrey Pines Scenic Drive, Sanford Consortium for Regenerative Medicine, Room 3102
|
| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
|
| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE216233 |
Beta cell dysfunction and dedifferentiation induced by Bone Morphogenetic Protein (BMP)-2 is associated with histone modifications and decreased NeuroD1 chromatin binding |
|
| Relations |
| BioProject |
PRJNA892633 |
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