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Identification of p...
Identification of proliferative and mature beta-cells in the islets of Langerhans
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- Bader, Erik (author)
- 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.
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- Migliorini, Adriana (author)
- Helmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Stem Cell Res, D-85764 Neuherberg, Germany.
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- Gegg, Moritz (author)
- Helmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Stem Cell Res, D-85764 Neuherberg, Germany.
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- Moruzzi, Noah (author)
- Helmholtz 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, Jantje (author)
- Helmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.
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- Roscioni, Sara S. (author)
- Helmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.
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- Bakhti, Mostafa (author)
- Helmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.
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- Brandl, Elisabeth (author)
- Helmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.
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- Irmler, Martin (author)
- German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Expt Genet, D-85764 Neuherberg, Germany.
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- Beckers, Johannes (author)
- 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.
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- Aichler, Michaela (author)
- Helmholtz Zentrum Munchen, Res Unit Analyt Pathol, D-85764 Neuherberg, Germany.
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- Feuchtinger, Annette (author)
- Helmholtz Zentrum Munchen, Res Unit Analyt Pathol, D-85764 Neuherberg, Germany.
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- Leitzinger, Christin (author)
- Helmholtz Zentrum Munchen, Inst Mol Toxicol & Pharmacol, D-85764 Neuherberg, Germany.
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- Zischka, Hans (author)
- Helmholtz Zentrum Munchen, Inst Mol Toxicol & Pharmacol, D-85764 Neuherberg, Germany.
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- Wang-Sattler, Rui (author)
- Helmholtz Zentrum Munchen, Inst Epidemiol 2, D-85764 Neuherberg, Germany.
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- Jastroch, Martin (author)
- German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Diabet & Obes, D-85764 Neuherberg, Germany.
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- Tschoep, Matthias (author)
- German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Diabet & Obes, D-85764 Neuherberg, Germany.
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- Machicao, Fausto (author)
- German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.;Univ Tubingen, Helmholtz Zentrum Munchen, Inst Diabet Res & Metab Dis, D-72076 Tubingen, Germany.
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- Staiger, Harald (author)
- 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.
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- Haering, Hans-Ulrich (author)
- 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.
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- Chmelova, Helena (author)
- 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.
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- Chouinard, Julie A. (author)
- 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.
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- Oskolkov, Nikolay (author)
- Lund Univ, Ctr Diabet, Diabet & Endocrinol, S-20502 Malmo, Sweden.
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- Korsgren, Olle (author)
- Uppsala universitet,Klinisk immunologi
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- Speier, Stephan (author)
- 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.
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- Lickert, Heiko (author)
- 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.
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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)
- 2016-07-11
- 2016
- English.
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 535:7612, s. 430-
- Related links:
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Abstract
Subject headings
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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
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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Nature
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- By the author/editor
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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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show more...
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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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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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Nature
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Uppsala University