Mouse pancreatic endocrine cell transcriptome defined in the embryonic Ngn3-null mouse.
OBJECTIVE
To document the transcriptome of the pancreatic islet during the early and late development of the mouse pancreas and highlight the qualitative and quantitative features of gene expression that contribute to the specification, growth, and differentiation of the major endocrine cell types. A further objective was to identify endocrine cell biomarkers, targets of diabetic autoimmunity, and regulatory pathways underlying islet responses to physiological and pathological stimuli.


METHODS
mRNA expression profiling was performed by microarray analysis of e12.5-18.5 embryonic pancreas from neurogenin 3 (Ngn3)-null mice, a background that abrogates endocrine pancreatic differentiation. The intersection of this data with mRNA expression in isolated adult pancreatic islets and pancreatic endocrine tumor cell lines was determined to compile lists of genes that are specifically expressed in endocrine cells.


RESULTS
The data provided insight into the transcriptional and morphogenetic factors that may play major roles in patterning and differentiation of the endocrine lineage before and during the secondary transition of endocrine development, as well as genes that control the glucose responsiveness of the beta-cells and candidate diabetes autoantigens, such as insulin, IA-2 and Slc30a8 (ZnT8). The results are presented as downloadable gene lists, available at https://www.cbil.upenn.edu/RADQuerier/php/displayStudy.php?study_id=1330, stratified by predictive scores of relative cell-type specificity.


CONCLUSIONS
The deposited data provide a rich resource that can be used to address diverse questions related to islet developmental and cell biology and the pathogenesis of type 1 and 2 diabetes.
Juhl
Kirstine
K
Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado, USA.
Sarkar
Suparna A
SA
Wong
Randall
R
Jensen
Jan
J
Hutton
John C
JC
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling / Q000379:methods*; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010179:Pancreas / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000075703:Zinc Transporter 8
D051792:Basic Helix-Loop-Helix Proteins; D027682:Cation Transport Proteins; D007328:Insulin; D009419:Nerve Tissue Proteins; D000075703:Zinc Transporter 8; C407737:Neurog3 protein, mouse; C516348:Slc30a8 protein, mouse