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FältnamnIndikatorerMetadata
00008133naa a2200589 4500
001oai:DiVA.org:uu-308258
003SwePub
008161124s2016 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3082582 URI
0247 a https://doi.org/10.1038/nature186242 DOI
040 a (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Bader, Eriku Helmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Stem Cell Res, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Epidemiol 2, D-85764 Neuherberg, Germany.4 aut
2451 0a Identification of proliferative and mature beta-cells in the islets of Langerhans
264 c 2016-07-11
264 1b Springer Science and Business Media LLC,c 2016
338 a print2 rdacarrier
520 a Insulin-dependent diabetes is a complex multifactorial disorder characterized by loss or dysfunction of beta-cells. Pancreatic beta-cells differ in size, glucose responsiveness, insulin secretion and precursor cell potential(1-5); understanding the mechanisms that underlie this functional heterogeneity might make it possible to develop new regenerative approaches. Here we show that Fltp (also known as Flattop and Cfap126), a Wnt/planar cell polarity (PCP) effector and reporter gene(6), acts as a marker gene that subdivides endocrine cells into two subpopulations and distinguishes proliferation-competent from mature beta-cells with distinct molecular, physiological and ultrastructural features. Genetic lineage tracing revealed that endocrine subpopulations from Fltp-negative and -positive lineages react differently to physiological and pathological changes. The expression of Fltp increases when endocrine cells cluster together to form polarized and mature 3D islet mini-organs(7-9). We show that 3D architecture and Wnt/PCP ligands are sufficient to trigger beta-cell maturation. By contrast, the Wnt/PCP effector Fltp is not necessary for beta-cell development, proliferation or maturation. We conclude that 3D architecture and Wnt/PCP signalling underlie functional beta-cell heterogeneity and induce beta-cell maturation. The identification of Fltp as a marker for endocrine subpopulations sheds light on the molecular underpinnings of islet cell heterogeneity and plasticity and might enable targeting of endocrine subpopulations for the regeneration of functional beta-cell mass in diabetic patients.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Cell- och molekylärbiologi0 (SwePub)301082 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Cell and Molecular Biology0 (SwePub)301082 hsv//eng
7001 a Migliorini, Adrianau Helmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Stem Cell Res, D-85764 Neuherberg, Germany.4 aut
7001 a Gegg, Moritzu Helmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Stem Cell Res, D-85764 Neuherberg, Germany.4 aut
7001 a Moruzzi, Noahu Helmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.;Karolinska Univ Hosp, Dept Mol Med & Surg, SE-17176 Stockholm, Sweden.4 aut
7001 a Gerdes, Jantjeu Helmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.4 aut
7001 a Roscioni, Sara S.u Helmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.4 aut
7001 a Bakhti, Mostafau Helmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.4 aut
7001 a Brandl, Elisabethu Helmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.4 aut
7001 a Irmler, Martinu German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Expt Genet, D-85764 Neuherberg, Germany.4 aut
7001 a Beckers, Johannesu German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Expt Genet, D-85764 Neuherberg, Germany.;Tech Univ Munich, Ismaninger Str 22, D-81675 Munich, Germany.4 aut
7001 a Aichler, Michaelau Helmholtz Zentrum Munchen, Res Unit Analyt Pathol, D-85764 Neuherberg, Germany.4 aut
7001 a Feuchtinger, Annetteu Helmholtz Zentrum Munchen, Res Unit Analyt Pathol, D-85764 Neuherberg, Germany.4 aut
7001 a Leitzinger, Christinu Helmholtz Zentrum Munchen, Inst Mol Toxicol & Pharmacol, D-85764 Neuherberg, Germany.4 aut
7001 a Zischka, Hansu Helmholtz Zentrum Munchen, Inst Mol Toxicol & Pharmacol, D-85764 Neuherberg, Germany.4 aut
7001 a Wang-Sattler, Ruiu Helmholtz Zentrum Munchen, Inst Epidemiol 2, D-85764 Neuherberg, Germany.4 aut
7001 a Jastroch, Martinu German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Diabet & Obes, D-85764 Neuherberg, Germany.4 aut
7001 a Tschoep, Matthiasu German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Diabet & Obes, D-85764 Neuherberg, Germany.4 aut
7001 a Machicao, Faustou German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.;Univ Tubingen, Helmholtz Zentrum Munchen, Inst Diabet Res & Metab Dis, D-72076 Tubingen, Germany.4 aut
7001 a Staiger, Haraldu German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.;Univ Tubingen, Helmholtz Zentrum Munchen, Inst Diabet Res & Metab Dis, D-72076 Tubingen, Germany.;Univ Tubingen, Div Endocrinol Diabetol Vasc Dis Nephrol & Clin C, Dept Internal Med, D-72076 Tubingen, Germany.4 aut
7001 a Haering, Hans-Ulrichu German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.;Univ Tubingen, Helmholtz Zentrum Munchen, Inst Diabet Res & Metab Dis, D-72076 Tubingen, Germany.;Univ Tubingen, Div Endocrinol Diabetol Vasc Dis Nephrol & Clin C, Dept Internal Med, D-72076 Tubingen, Germany.4 aut
7001 a Chmelova, Helenau German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.;Tech Univ Dresden, Univ Clin Carl Gustav Carus, Helmholtz Zentrum Munchen, PLID, D-01307 Dresden, Germany.;Tech Univ Dresden, Fac Med, DFG Ctr Regenerat Therapies Dresden CRTD, D-01307 Dresden, Germany.4 aut
7001 a Chouinard, Julie A.u German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.;Tech Univ Dresden, Univ Clin Carl Gustav Carus, Helmholtz Zentrum Munchen, PLID, D-01307 Dresden, Germany.;Tech Univ Dresden, Fac Med, DFG Ctr Regenerat Therapies Dresden CRTD, D-01307 Dresden, Germany.4 aut
7001 a Oskolkov, Nikolayu Lund Univ, Ctr Diabet, Diabet & Endocrinol, S-20502 Malmo, Sweden.4 aut
7001 a Korsgren, Olleu Uppsala universitet,Klinisk immunologi4 aut0 (Swepub:uu)ollekors
7001 a Speier, Stephanu German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.;Tech Univ Dresden, Univ Clin Carl Gustav Carus, Helmholtz Zentrum Munchen, PLID, D-01307 Dresden, Germany.;Tech Univ Dresden, Fac Med, DFG Ctr Regenerat Therapies Dresden CRTD, D-01307 Dresden, Germany.4 aut
7001 a Lickert, Heikou Helmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Stem Cell Res, D-85764 Neuherberg, Germany.;German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.;Tech Univ Munich, Ismaninger Str 22, D-81675 Munich, Germany.4 aut
7102 a Helmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Stem Cell Res, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Epidemiol 2, D-85764 Neuherberg, Germany.b Helmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Stem Cell Res, D-85764 Neuherberg, Germany.4 org
7730 t Natured : Springer Science and Business Media LLCg 535:7612, s. 430-+q 535:7612<430-+x 0028-0836x 1476-4687
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-308258
8564 8u https://doi.org/10.1038/nature18624

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