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Status |
Public on Sep 01, 2015 |
Title |
RNA sequencing of pancreatic islets and islet-derived macrophages and endothelial cells modulated by vascular endothelial growth factor-A signaling |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Pancreatic islet endocrine cell and endothelial cell (EC) interactions mediated by vascular endothelial growth factor-A (VEGF-A) signaling are important for islet endocrine cell differentiation and the formation of highly vascularized islets. To dissect how VEGF-A signaling modulates intra-islet vasculature and innervation, islet microenvironment, and β cell mass, we transiently increased VEGF-A production by β cells. VEGF-A induction dramatically increased the number of intra-islet ECs but led to β cell loss. After withdrawal of the VEGF-A stimulus, β cell mass, function, and islet structure normalized as a result of a robust, but transient, burst in proliferation of pre-existing β cells. Bone marrow-derived macrophages (MΦs) recruited to the site of β cell injury were crucial for the β cell proliferation, which was independent of pancreatic location and circulating factors such as glucose. Identification of the signals responsible for the proliferation of adult, terminally differentiated β cells will improve strategies aimed at β cell regeneration and expansion.
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Overall design |
Examination of RNA profiles from isolated whole islets from RIP-rtTA; TetO-VEGF-A mice with no doxycycline (Dox) treatment (3 samples) and after 1 week of Dox (3 sample); and islet-derived macrophages (3 samples) and endothelial cells (3 samples) isolated from dispersed purified islets from RIP-rtTA; TetO-VEGF-A mice after 1 week Dox treatment by fluorescence-activated cell sorting using antibodies against CD11b and CD31, respectively.
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Contributor(s) |
Powers AC, Brissova M |
Citation(s) |
24561261, 24574008, 33824346 |
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Submission date |
Aug 31, 2015 |
Last update date |
Apr 28, 2021 |
Contact name |
Alvin C Powers |
Organization name |
Vanderbilt University Medical Center
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Department |
Medicine
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Street address |
2213 Garland Avenue
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City |
Nashville |
State/province |
Tennessee |
ZIP/Postal code |
37232 |
Country |
USA |
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Platforms (1) |
GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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Samples (12)
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Relations |
BioProject |
PRJNA294308 |
SRA |
SRP063013 |