title: The NOTCH pathway in β-cell growth and differentiation.
abstract: Beta-cell replacement represents the optimal therapy for type 1 diabetes. Efforts to manipulate β-cell proliferation and differentiation could be advanced by a better understanding of the normal pathways regulating β-cell development and renewal. NOTCH signaling is a highly conserved pathway which plays a central role in pancreas development. Cell-lineage tracing has revealed the reactivation of the NOTCH pathway in adult human β cells cultured under conditions which induce cell proliferation and dedifferentiation. Inhibition of NOTCH signaling in dedifferentiated cells following ex vivo expansion has been shown to promote restoration of the β-cell phenotype. This approach may increase the availability of functional β cells for transplantation.
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Bar
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: sefrat@post.tau.ac.il.
authors.forename: Shimon
authors.initials: S
authors.lastname: Efrat
mesh_terms: D000818:Animals; D054337:Cell Dedifferentiation; D002454:Cell Differentiation; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D008024:Ligands; D008954:Models, Biological; D020033:Protein Isoforms / Q000819:agonists / Q000378:metabolism; D051880:Receptors, Notch / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D008024:Ligands; D020033:Protein Isoforms; D051880:Receptors, Notch
keywords: Cell transplantation; Diabetes; HES1; Insulin; Islet cell proliferation; Pancreas development; Redifferentiation