title: Islet Pericytes Are Required for β-Cell Maturity.
abstract: β-Cells rely on the islet microenvironment for their functionality and mass. Pericytes, along with endothelial cells, make up the dense islet capillary network. However, although the role of endothelial cells in supporting β-cell homeostasis has been vastly investigated, the role of pericytes remains largely unknown. Here, we focus on contribution of pericytes to β-cell function. To this end, we used a transgenic mouse system that allows diphtheria toxin-based depletion of pericytes. Our results indicate that islets depleted of their pericytes have reduced insulin content and expression. Additionally, isolated islets displayed impaired glucose-stimulated insulin secretion, accompanied by a reduced expression of genes associated with β-cell function. Importantly, reduced levels of the transcription factors MafA and Pdx1 point to β-cell dedifferentiation in the absence of pericytes. Ex vivo depletion of pericytes in isolated islets resulted in a similar impairment of gene expression, implicating their direct, blood flow-independent role in maintaining β-cell maturity. To conclude, our findings suggest that pericytes are pivotal components of the islet niche, which are required for β-cell maturity and functionality. Abnormalities of islet pericytes, as implicated in type 2 diabetes, may therefore contribute to β-cell dysfunction and disease progression.
authors.affiliation: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Sasson
authors.affiliation: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Eleonor
authors.initials: E
authors.lastname: Rachi
authors.affiliation: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Lina
authors.initials: L
authors.lastname: Sakhneny
authors.affiliation: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Daria
authors.initials: D
authors.lastname: Baer
authors.affiliation: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Lisnyansky
authors.affiliation: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Alona
authors.initials: A
authors.lastname: Epshtein
authors.affiliation: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel limorl@post.tau.ac.il.
authors.forename: Limor
authors.initials: L
authors.lastname: Landsman
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism*; D051473:Maf Transcription Factors, Large / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D020286:Pericytes / Q000166:cytology* / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; C485159:MAFA protein, human; D051473:Maf Transcription Factors, Large; C107965:Nkx3-2 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C084010:pancreatic and duodenal homeobox 1 protein