Identification of proliferative and mature β-cells in the islets of Langerhans - PubMed (original) (raw)
. 2016 Jul 21;535(7612):430-4.
doi: 10.1038/nature18624. Epub 2016 Jul 11.
Adriana Migliorini, Moritz Gegg, Noah Moruzzi, Jantje Gerdes, Sara S Roscioni, Mostafa Bakhti, Elisabeth Brandl, Martin Irmler, Johannes Beckers, Michaela Aichler, Annette Feuchtinger, Christin Leitzinger, Hans Zischka, Rui Wang-Sattler, Martin Jastroch, Matthias Tschöp, Fausto Machicao, Harald Staiger, Hans-Ulrich Häring, Helena Chmelova, Julie A Chouinard, Nikolay Oskolkov, Olle Korsgren, Stephan Speier, Heiko Lickert
- PMID: 27398620
- DOI: 10.1038/nature18624
Identification of proliferative and mature β-cells in the islets of Langerhans
Erik Bader et al. Nature. 2016.
Abstract
Insulin-dependent diabetes is a complex multifactorial disorder characterized by loss or dysfunction of β-cells. Pancreatic β-cells differ in size, glucose responsiveness, insulin secretion and precursor cell potential; 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 acts as a marker gene that subdivides endocrine cells into two subpopulations and distinguishes proliferation-competent from mature β-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. We show that 3D architecture and Wnt/PCP ligands are sufficient to trigger β-cell maturation. By contrast, the Wnt/PCP effector Fltp is not necessary for β-cell development, proliferation or maturation. We conclude that 3D architecture and Wnt/PCP signalling underlie functional β-cell heterogeneity and induce β-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 β-cell mass in diabetic patients.
Comment in
- Physiology: Pancreatic β-cell heterogeneity revisited.
Bonner-Weir S, Aguayo-Mazzucato C. Bonner-Weir S, et al. Nature. 2016 Jul 21;535(7612):365-6. doi: 10.1038/nature18907. Epub 2016 Jul 13. Nature. 2016. PMID: 27398615 No abstract available. - Diabetes: β-cell heterogeneity - key to unlocking islet regeneration.
Holmes D. Holmes D. Nat Rev Endocrinol. 2016 Sep;12(9):495. doi: 10.1038/nrendo.2016.122. Epub 2016 Jul 22. Nat Rev Endocrinol. 2016. PMID: 27448053 No abstract available. - Heterogeneity of β-cells.
Kume S. Kume S. J Diabetes Investig. 2017 Sep;8(5):656-657. doi: 10.1111/jdi.12608. Epub 2017 Jan 31. J Diabetes Investig. 2017. PMID: 27930878 Free PMC article.
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