Search: onr:"swepub:oai:DiVA.org:uu-308258" >
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Bader, ErikHelmholtz 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.
(author)
Identification of proliferative and mature beta-cells in the islets of Langerhans
- Article/chapterEnglish2016
Publisher, publication year, extent ...
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2016-07-11
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Springer Science and Business Media LLC,2016
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-308258
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-308258URI
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https://doi.org/10.1038/nature18624DOI
Supplementary language notes
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Language:English
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Summary in:English
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Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Migliorini, AdrianaHelmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Stem Cell Res, D-85764 Neuherberg, Germany.
(author)
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Gegg, MoritzHelmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Stem Cell Res, D-85764 Neuherberg, Germany.
(author)
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Moruzzi, NoahHelmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.;Karolinska Univ Hosp, Dept Mol Med & Surg, SE-17176 Stockholm, Sweden.
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Gerdes, JantjeHelmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.
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Roscioni, Sara S.Helmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.
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Bakhti, MostafaHelmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.
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Brandl, ElisabethHelmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.
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Irmler, MartinGerman Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Expt Genet, D-85764 Neuherberg, Germany.
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Beckers, JohannesGerman 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.
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Aichler, MichaelaHelmholtz Zentrum Munchen, Res Unit Analyt Pathol, D-85764 Neuherberg, Germany.
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Feuchtinger, AnnetteHelmholtz Zentrum Munchen, Res Unit Analyt Pathol, D-85764 Neuherberg, Germany.
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Leitzinger, ChristinHelmholtz Zentrum Munchen, Inst Mol Toxicol & Pharmacol, D-85764 Neuherberg, Germany.
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Zischka, HansHelmholtz Zentrum Munchen, Inst Mol Toxicol & Pharmacol, D-85764 Neuherberg, Germany.
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Wang-Sattler, RuiHelmholtz Zentrum Munchen, Inst Epidemiol 2, D-85764 Neuherberg, Germany.
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Jastroch, MartinGerman Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Diabet & Obes, D-85764 Neuherberg, Germany.
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Tschoep, MatthiasGerman Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Diabet & Obes, D-85764 Neuherberg, Germany.
(author)
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Machicao, FaustoGerman Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.;Univ Tubingen, Helmholtz Zentrum Munchen, Inst Diabet Res & Metab Dis, D-72076 Tubingen, Germany.
(author)
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Staiger, HaraldGerman 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.
(author)
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Haering, Hans-UlrichGerman 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.
(author)
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Chmelova, HelenaGerman 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.
(author)
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Chouinard, Julie A.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.
(author)
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Oskolkov, NikolayLund Univ, Ctr Diabet, Diabet & Endocrinol, S-20502 Malmo, Sweden.
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Korsgren, OlleUppsala universitet,Klinisk immunologi(Swepub:uu)ollekors
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Speier, StephanGerman 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.
(author)
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Lickert, HeikoHelmholtz 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.
(author)
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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.Helmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Stem Cell Res, D-85764 Neuherberg, Germany.
(creator_code:org_t)
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In:Nature: Springer Science and Business Media LLC535:7612, s. 430-+0028-08361476-4687
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Bader, Erik
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Migliorini, Adri ...
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Gegg, Moritz
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Moruzzi, Noah
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Gerdes, Jantje
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Roscioni, Sara S ...
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Bakhti, Mostafa
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Brandl, Elisabet ...
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Irmler, Martin
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Beckers, Johanne ...
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Aichler, Michael ...
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Feuchtinger, Ann ...
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Leitzinger, Chri ...
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Zischka, Hans
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Wang-Sattler, Ru ...
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Jastroch, Martin
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Tschoep, Matthia ...
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Machicao, Fausto
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Staiger, Harald
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Haering, Hans-Ul ...
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Chmelova, Helena
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Chouinard, Julie ...
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Oskolkov, Nikola ...
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Korsgren, Olle
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Speier, Stephan
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Lickert, Heiko
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