Transcriptomics

Dataset Information

3

Identification of proliferative and mature β-cells in the islet of Langerhans


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 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.

ORGANISM(S): Mus musculus  

SUBMITTER: Hans U Haering   Moritz Gegg  Christin Leitzinger  Erik Bader  Martin Irmler  Adriana Migliorini  Rui Wang-Sattler  Hans Zischka  Harald Staiger  Julie Chouinard  Stephan Speier  Helena Chmelova  Mostafa Bakhti  Annette Feuchtinger  Jantje Gerdes  Johannes Beckers  Noah Moruzzi  Michaela Aichler  Fausto Machicao  Heiko Lickert 

PROVIDER: E-GEOD-68853 | ArrayExpress | 2016-06-02

SECONDARY ACCESSION(S): GSE68853PRJNA283903

REPOSITORIES: GEO, ArrayExpress

Similar Datasets

2019-11-13 | PXD012081 | Pride
| GSE109285 | GEO
2014-09-04 | E-GEOD-61090 | ArrayExpress
| GSE61180 | GEO
2014-09-06 | E-GEOD-61180 | ArrayExpress
2014-09-06 | E-GEOD-61181 | ArrayExpress
2014-09-06 | E-GEOD-61179 | ArrayExpress
| GSE102027 | GEO
2014-09-25 | E-GEOD-61714 | ArrayExpress
2014-07-31 | E-GEOD-59928 | ArrayExpress