title: Targeting insulin-producing beta cells for regenerative therapy.
abstract: Pancreatic beta cells differ in terms of glucose responsiveness, insulin secretion and proliferative capacity; however, the molecular pathways that regulate this cellular heterogeneity are unknown. We have identified the Wnt-planar cell polarity (PCP) effector Flattop (FLTP) as a biomarker that identifies mature beta cells in the islets of Langerhans. Interestingly, three-dimensional architecture and Wnt-PCP ligands are sufficient to trigger mouse and human beta cell maturation. These results highlight the fact that novel biomarkers shed light on the long-standing mystery of beta cell heterogeneity and identify the Wnt-PCP pathway as triggering beta cell maturation. Understanding heterogeneity in the islets of Langerhans might allow targeting of beta cell subpopulations for regenerative therapy and provide building principles for stem cell-derived islets. This review summarises a presentation given at the 'Can we make a better beta cell?' symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Amin Ardestani and Kathrin Maedler, DOI: 10.1007/s00125-016-3892-9 , and by Harry Heimberg and colleagues, DOI: 10.1007/s00125-016-3879-6 ) and a commentary by the Session Chair, Shanta Persaud (DOI: 10.1007/s00125-016-3870-2 ).
authors.affiliation: Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, Ingolstädter Landstr. 1, D-85764, Neuherberg, Germany.|German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors.forename: Adriana
authors.initials: A
authors.lastname: Migliorini
authors.affiliation: Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, Ingolstädter Landstr. 1, D-85764, Neuherberg, Germany.|German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors.forename: Sara S
authors.initials: SS
authors.lastname: Roscioni
authors.affiliation: Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, Ingolstädter Landstr. 1, D-85764, Neuherberg, Germany. heiko.lickert@helmholtz-muenchen.de.|Institute of Stem Cell Research, Helmholtz Zentrum München, Munich, Germany. heiko.lickert@helmholtz-muenchen.de.|German Center for Diabetes Research (DZD), Neuherberg, Germany. heiko.lickert@helmholtz-muenchen.de.
authors.forename: Heiko
authors.initials: H
authors.lastname: Lickert
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism*; D007515:Islets of Langerhans / Q000166:cytology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology
chemical_list: D008869:Microtubule-Associated Proteins
keywords: Beta cell heterogeneity; Cell-replacement therapy; Dedifferentiation; Islet architecture; Maturation; Plasticity; Regenerative therapy; Wnt signalling