RNA sequencing of pancreatic islet-derived beta cells, macrophages, and endothelial cells modulated by vascular endothelial growth factor-A signaling

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 beta cell mass, we transiently increased VEGF-A production by beta cells. VEGF-A induction dramatically increased the number of intra-islet ECs but led to beta cell loss. After withdrawal of the VEGF-A stimulus, beta cell mass, function, and islet structure normalized as a result of a robust, but transient, burst in proliferation of pre-existing beta cells. Bone marrow-derived macrophages recruited to the site of beta cell injury were crucial for the beta 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 beta cells will improve strategies aimed at beta cell regeneration and expansion. Examination of RNA profiles from islet-derived beta cells (12 samples), endothelial cells (10 samples), and macrophages (10 samples) from MIP-GFP; RIP-rtTA; TetO-VEGF-A mice with no doxycycline (Dox) treatment (12 samples), after 1 week of Dox (8 samples), and after 1 week of Dox withdrawal (12 samples); cells were isolated by fluorescence-activated cell sorting using GFP for beta cells (MIP-GFP) and antibodies against CD31 abd CD11b for endothelial cells and macrophages, respectively. Related to GSE72546.