Please note that we have stopped the regular imports of Gene Expression Omnibus (GEO) data into ArrayExpress. This may not be the latest version of this experiment.
E-GEOD-68853 - Identification of proliferative and mature β-cells in the islet of Langerhans
Released on 2 June 2016, last updated on 3 June 2016
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 potential1-5, thus understanding the mechanisms underlying this functional heterogeneity might allow novel regenerative approaches. Here we discovered Flattop (Fltp) as a biomarker that distinguishes proliferative from mature β-cells. Genetic lineage tracing revealed that these β-cell subpopulations react differentially to environmental changes. Upon insulin resistance Fltp- β-cells undergo compensatory proliferation, whereas Fltp-lineage+ β-cells account for islet cell hypertrophy commonly associated with cytotoxic stress. The expression of the Wnt/planar cell polarity (PCP) effector gene Fltp increases when naïve β-cells cluster together to form polarized and mature three-dimensional (3D) islet mini-organs6-8. We show that dispersed early postnatal islet cells, insulinoma cells and human β-cells all have the intrinsic ability to form polarized pseudo-islets in 3D cultures. Compaction and polarization correlates with the induction of maturation markers and can be enhanced by Wnt/PCP pathway activation. Finally, we show that Fltp is not only a marker for mature β-cells, but is also functionally required for proper insulin secretion in mouse and human. We conclude that planar cell polarity and 3D architecture underlie functional β-cell heterogeneity and report that Fltp is a biomarker that separates proliferative from mature β-cells. These findings establish novel molecular underpinnings of β-cells and enable targeting of subpopulations for the regeneration of functional β-cell mass in diabetic patients. We performed gene expression microarray analysis on two FACS-sorted pancreatic islet cell populations: flattop-positive and flattop-negative.
transcription profiling by array
Johannes Beckers <email@example.com>, Adriana Migliorini, Annette Feuchtinger, Christin Leitzinger, Erik Bader, Fausto Machicao, Hans U Haering, Hans Zischka, Harald Staiger, Heiko Lickert, Helena Chmelova, Jantje Gerdes, Julie Chouinard, Martin Irmler, Michaela Aichler, Moritz Gegg, Mostafa Bakhti, Noah Moruzzi, Rui Wang-Sattler, Stephan Speier