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Mouse pancreatic endocrine cell transcriptome defined in the embryonic Ngn3- mouse.

Juhl K, Sarkar SA, Wong R, Jensen J, Hutton JC - Diabetes (2008)

Bottom Line: A further objective was to identify endocrine cell biomarkers, targets of diabetic autoimmunity, and regulatory pathways underlying islet responses to physiological and pathological stimuli. mRNA expression profiling was performed by microarray analysis of e12.5-18.5 embryonic pancreas from neurogenin 3 (Ngn3)- 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.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).

View Article: PubMed Central - PubMed

Affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado, USA.

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)- 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.

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Related in: MedlinePlus

Immunofluorescent detection of ZnT8. E18.5 wild-type mouse pancreas incubated with guinea pig anti-insulin (Ins, green), rabbit anti-ZnT8 (red), mouse anti-glucagon (Gcg, blue), and rat anti-somatostatin (SST, white) antibodies were developed with secondary antibodies linked to Alexa 488, Cy3, 1-amino-1-methyl-3(4)-aminomethylcyclohexane, and Cy5, respectively. ZnT8 colocalized with insulin and somatostatin-expressing cells. Scale bar = 10 μm. (Please see http://dx.doi.org.10.2337/db07-1126 for a high-quality digital representation of this figure.)
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f2: Immunofluorescent detection of ZnT8. E18.5 wild-type mouse pancreas incubated with guinea pig anti-insulin (Ins, green), rabbit anti-ZnT8 (red), mouse anti-glucagon (Gcg, blue), and rat anti-somatostatin (SST, white) antibodies were developed with secondary antibodies linked to Alexa 488, Cy3, 1-amino-1-methyl-3(4)-aminomethylcyclohexane, and Cy5, respectively. ZnT8 colocalized with insulin and somatostatin-expressing cells. Scale bar = 10 μm. (Please see http://dx.doi.org.10.2337/db07-1126 for a high-quality digital representation of this figure.)

Mentions: Immunohistochemical localization of ZnT8 in wild-type adult pancreas showed its expression in the majority of islet cells and absence in acinar and ductal tissue. It was principally colocalized with insulin and also found in a subpopulation of somatostatin-positive cells. Expression in α-cells was not detectable (Fig. 2). E18.5 Ngn3−/− pancreas tissue did not show any ZnT8, insulin, glucagon, or somatostatin expression (data not shown).


Mouse pancreatic endocrine cell transcriptome defined in the embryonic Ngn3- mouse.

Juhl K, Sarkar SA, Wong R, Jensen J, Hutton JC - Diabetes (2008)

Immunofluorescent detection of ZnT8. E18.5 wild-type mouse pancreas incubated with guinea pig anti-insulin (Ins, green), rabbit anti-ZnT8 (red), mouse anti-glucagon (Gcg, blue), and rat anti-somatostatin (SST, white) antibodies were developed with secondary antibodies linked to Alexa 488, Cy3, 1-amino-1-methyl-3(4)-aminomethylcyclohexane, and Cy5, respectively. ZnT8 colocalized with insulin and somatostatin-expressing cells. Scale bar = 10 μm. (Please see http://dx.doi.org.10.2337/db07-1126 for a high-quality digital representation of this figure.)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2551686&req=5

f2: Immunofluorescent detection of ZnT8. E18.5 wild-type mouse pancreas incubated with guinea pig anti-insulin (Ins, green), rabbit anti-ZnT8 (red), mouse anti-glucagon (Gcg, blue), and rat anti-somatostatin (SST, white) antibodies were developed with secondary antibodies linked to Alexa 488, Cy3, 1-amino-1-methyl-3(4)-aminomethylcyclohexane, and Cy5, respectively. ZnT8 colocalized with insulin and somatostatin-expressing cells. Scale bar = 10 μm. (Please see http://dx.doi.org.10.2337/db07-1126 for a high-quality digital representation of this figure.)
Mentions: Immunohistochemical localization of ZnT8 in wild-type adult pancreas showed its expression in the majority of islet cells and absence in acinar and ductal tissue. It was principally colocalized with insulin and also found in a subpopulation of somatostatin-positive cells. Expression in α-cells was not detectable (Fig. 2). E18.5 Ngn3−/− pancreas tissue did not show any ZnT8, insulin, glucagon, or somatostatin expression (data not shown).

Bottom Line: A further objective was to identify endocrine cell biomarkers, targets of diabetic autoimmunity, and regulatory pathways underlying islet responses to physiological and pathological stimuli. mRNA expression profiling was performed by microarray analysis of e12.5-18.5 embryonic pancreas from neurogenin 3 (Ngn3)- 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.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).

View Article: PubMed Central - PubMed

Affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado, USA.

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)- 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.

Show MeSH
Related in: MedlinePlus