Mouse Pancreatic Endocrine Cell Transcriptome Defined in the Embryonic Ngn3-Null Mouse

Abstract

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. RESEARCH DESIGN AND 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 β-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.

Intraislet SLIT–ROBO signaling is required for beta-cell survival and potentiates insulin secretion

“…The mammalian genome contains three Slit ligands and four Robo receptors. Our bioinformatic studies identified the expression of several Slit and Robo family members in adult human and rodent pancreatic islet cells (12), and Robo1 was identified by others as a transcript enriched in pancreatic endocrine cells during development (22). Nevertheless, no in-depth studies of these proteins have been reported.…”

Aging induces a distinct gene expression program in mouse islets

“…heterogeneous nuclear ribonucleoprotein A/B; Abbp1) is a heterogeneous nuclear ribonucleoprotein that is expressed in the developing endocrine pancreas. 45 Other notable genes downregulated by partial pancreatectomy include insulin 2 (1.7 fold reduced).…”

Downregulation of ZnT8 expression in pancreatic β-cells of diabetic mice

“…Some reported that ZnT8 is expressed in alpha cells, while other groups indicated that ZnT8 is expressed in d cells but not in a cells. [17][18][19] As an initial step toward elucidating the roles of ZnT8 in islet homeostasis and pathophysiology of type 2 diabetes, we examined ZnT8 expression profile during pancreas development, in wild-type adult mouse islet cells and in the endocrine islets of diabetic mouse models.…”