title: Clusters of conserved beta cell marker genes for assessment of beta cell phenotype.
abstract: METHODS
  The aim of this study was to establish a gene expression blueprint of pancreatic beta cells conserved from rodents to humans and to evaluate its applicability to assess shifts in the beta cell differentiated state. Genome-wide mRNA expression profiles of isolated beta cells were compared to those of a large panel of other tissue and cell types, and transcripts with beta cell-abundant and -selective expression were identified. Iteration of this analysis in mouse, rat and human tissues generated a panel of conserved beta cell biomarkers. This panel was then used to compare isolated versus laser capture microdissected beta cells, monitor adaptations of the beta cell phenotype to fasting, and retrieve possible conserved transcriptional regulators.
  
  
  RESULTS
  A panel of 332 conserved beta cell biomarker genes was found to discriminate both isolated and laser capture microdissected beta cells from all other examined cell types. Of all conserved beta cell-markers, 15% were strongly beta cell-selective and functionally associated to hormone processing, 15% were shared with neuronal cells and associated to regulated synaptic vesicle transport and 30% with immune plus gut mucosal tissues reflecting active protein synthesis. Fasting specifically down-regulated the latter cluster, but preserved the neuronal and strongly beta cell-selective traits, indicating preserved differentiated state. Analysis of consensus binding site enrichment indicated major roles of CREB/ATF and various nutrient- or redox-regulated transcription factors in maintenance of differentiated beta cell phenotype.
  
  
  CONCLUSIONS
  Conserved beta cell marker genes contain major gene clusters defined by their beta cell selectivity or by their additional abundance in either neural cells or in immune plus gut mucosal cells. This panel can be used as a template to identify changes in the differentiated state of beta cells.
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium. geert.martens@vub.ac.be
authors.forename: Geert A
authors.initials: GA
authors.lastname: Martens
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.forename: Karine H
authors.initials: KH
authors.lastname: Hellemans
authors.forename: Geert
authors.initials: G
authors.lastname: Stangé
authors.forename: Harry
authors.initials: H
authors.lastname: Heimberg
authors.forename: Finn C
authors.initials: FC
authors.lastname: Nielsen
authors.forename: Olivier
authors.initials: O
authors.lastname: Sand
authors.forename: Jacques
authors.initials: J
authors.lastname: Van Helden
authors.forename: Leentje
authors.initials: L
authors.lastname: Van Lommel
authors.forename: Frans
authors.initials: F
authors.lastname: Schuit
authors.forename: Frans K
authors.initials: FK
authors.lastname: Gorus
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Pipeleers
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D017124:Conserved Sequence; D005215:Fasting / Q000378:metabolism; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D005810:Multigene Family / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D014157:Transcription Factors