{"doi":"10.1101/2020.08.28.265728","title":"Coordinated interactions between endothelial cells and macrophages in the islet microenvironment promote β cell regeneration","abstract":"ABSTRACT Endogenous β cell regeneration could alleviate diabetes, but proliferative stimuli within the islet microenvironment are incompletely understood. We previously found that β cell recovery following hypervascularization-induced β cell loss involves interactions with endothelial cells (ECs) and macrophages (MΦs). Here we show that proliferative ECs modulate MΦ infiltration and phenotype during β cell loss, and recruited MΦs are essential for β cell recovery. Furthermore, VEGFR2 inactivation in quiescent ECs accelerates islet vascular regression during β cell recovery and leads to increased β cell proliferation without changes in MΦ phenotype or number. Transcriptome analysis of β cells, ECs, and MΦs reveals that β cell proliferation coincides with elevated expression of extracellular matrix remodeling molecules and growth factors likely driving activation of proliferative signaling pathways in β cells. Collectively, these findings suggest a new β cell regeneration paradigm whereby coordinated interactions between intra-islet MΦs, ECs, and extracellular matrix mediate β cell self-renewal.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":130838,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":583651,"name":"Kristie Aamodt","orcid":"0000-0003-0065-0786","position":1,"is_corresponding":false},{"id":583652,"name":"Tiffany M. Richardson","orcid":"0000-0002-0272-6804","position":2,"is_corresponding":false},{"id":584066,"name":"Alec Hopkirk","orcid":null,"position":3,"is_corresponding":false},{"id":252942,"name":"Radhika Aramandla","orcid":null,"position":4,"is_corresponding":false},{"id":310412,"name":"Greg Poffenberger","orcid":"0000-0002-7363-4683","position":5,"is_corresponding":false},{"id":252943,"name":"Regina Jenkins","orcid":null,"position":6,"is_corresponding":false},{"id":269508,"name":"David K. Flaherty","orcid":null,"position":7,"is_corresponding":false},{"id":343975,"name":"Nripesh Prasad","orcid":"0000-0003-4074-2538","position":8,"is_corresponding":false},{"id":584067,"name":"Sean E. Levy","orcid":null,"position":9,"is_corresponding":false},{"id":7379,"name":"Alvin C. Powers","orcid":"0000-0003-1941-5786","position":10,"is_corresponding":false},{"id":250528,"name":"Marcela Briššová","orcid":"0000-0002-4999-3280","position":11,"is_corresponding":false},{"id":250523,"name":"Diane C. Saunders","orcid":"0000-0002-8849-6746","position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":null,"created_at":"2026-07-18T23:15:56.698770Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}