Comment[ArrayExpressAccession]	E-GEOD-68853
MAGE-TAB Version	1.1																					
Public Release Date	2016-06-02
Investigation Title	Identification of proliferative and mature β-cells in the islet of Langerhans																					
Comment[Submitted Name]	Identification of proliferative and mature β-cells in the islet of Langerhans
Experiment Description	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.																					
Term Source Name	ArrayExpress	EFO
Term Source File	http://www.ebi.ac.uk/arrayexpress/	http://www.ebi.ac.uk/efo/efo.owl																				
Person Last Name	Beckers	Bader	Migliorini	Gegg	Moruzzi	Gerdes	Bakhti	Irmler	Beckers	Aichler	Feuchtinger	Leitzinger	Zischka	Wang-Sattler	Machicao	Staiger	Haering	Chmelova	Chouinard	Moruzzi	Speier	Lickert
Person First Name	Johannes	Erik	Adriana	Moritz	Noah	Jantje	Mostafa	Martin	Johannes	Michaela	Annette	Christin	Hans	Rui	Fausto	Harald	Hans	Helena	Julie	Noah	Stephan	Heiko
Person Mid Initials																	U					
Person Email	beckers@helmholtz-muenchen.de																					
Person Affiliation	Helmholtz Zentrum Muenchen																					
Person Address	Institute of Experimental Genetics, Helmholtz Zentrum Muenchen, Ingolstaedter Landstr. 1, Neuherberg, Germany																					
Person Roles	submitter																					
Protocol Name	P-GSE68853-1	P-GSE68853-5	P-GSE68853-6	P-GSE68853-2	P-GSE68853-3	P-GSE68853-4	P-GSE68853-7															
Protocol Description	RMA probeset summary with standard settings of the Affymetrix Expression Console software (v.1.3.0.187) including median polish and Sketch-Quantile normalisation. ID_REF =  VALUE = RMA signal intensity (log2)	Ovation PicoSL WTA System V2 and Encore Biotin Module (Nugen).	According to the Affymetrix expression protocol (HWS kit).	No treatment.	Animals housed under spf conditions.	miRNeasy Micro Kit (Qiagen) including DNase treatment.	According to the Affymetrix expression protocol, Scanner 3000 7G.															
Protocol Type	normalization data transformation protocol	labelling protocol	hybridization protocol	sample treatment protocol	growth protocol	nucleic acid extraction protocol	array scanning protocol															
Experimental Factor Name	flattop status																					
Experimental Factor Type	flattop status																					
Comment[SecondaryAccession]	GSE68853																					
Comment[GEOReleaseDate]	2016-06-02																					
Comment[ArrayExpressSubmissionDate]	2015-05-13																					
Comment[GEOLastUpdateDate]	2016-06-02																					
Comment[AEExperimentType]	transcription profiling by array																					
SDRF File	E-GEOD-68853.sdrf.txt