Dataset Information

Nestin expression in pancreatic endocrine and exocrine cells of mice lacking glucagon signaling.

ABSTRACT: Nestin, a marker of neural stem cells, is also expressed by cells located in the epithelium of the pancreatic primordium and by a subpopulation of exocrine cells but not by endocrine cells. These findings raised the possibility that the pancreatic epithelium is heterogeneous and comprised of subpopulations of exocrine/nestin-positive and endocrine/nestin-negative precursor cells. We examined this issue in two mutant mouse models characterized by protracted expression of several embryonal properties in islet cells. One mutant line comprises mice lacking mature glucagon due to abrogation of proprotein convertase-2 (PC2(-/-)), responsible for the conversion of proglucagon into glucagon, while the second line consists of mice with a global deletion of the glucagon receptor (Gcgr(-/-)). We demonstrate that nestin is transiently expressed by acinar cells and by insulin and glucagon cells of islets of both lines of mice. In addition, the lack of glucagon signaling increased nestin mRNA levels in pancreas of mutant embryos and adult mice. We conclude that nestin+ cells located in the pancreatic primordium generate the cells of the endocrine and exocrine lineages. Furthermore, our results suggest that nestin expression is regulated by glucagon signaling.

SUBMITTER: Kedees MH

PROVIDER: S-EPMC4287279 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature

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Nestin expression in pancreatic endocrine and exocrine cells of mice lacking glucagon signaling.

Kedees Mamdouh H MH Guz Yelena Y Vuguin Patricia M PM Vargas Carlos C Cui Lingguang L Steiner Donald F DF Charron Maureen J MJ Teitelman Gladys G

Developmental dynamics : an official publication of the American Association of Anatomists 20070401 4

Nestin, a marker of neural stem cells, is also expressed by cells located in the epithelium of the pancreatic primordium and by a subpopulation of exocrine cells but not by endocrine cells. These findings raised the possibility that the pancreatic epithelium is heterogeneous and comprised of subpopulations of exocrine/nestin-positive and endocrine/nestin-negative precursor cells. We examined this issue in two mutant mouse models characterized by protracted expression of several embryonal propert ...[more]

PMID: 17366624

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Project description:The need for a clinically accessible method with the ability to match protein activity within heterogeneous tissues is currently unmet by existing technologies. Our proteomics sample preparation platform, named microPOTS (Microdroplet Processing in One pot for Trace Samples), can be used to measure relative protein abundance in micron-scale samples alongside the spatial location of each measurement, thereby tying biologically interesting proteins and pathways to distinct regions. However, given the smaller pixel/voxel number and amount of tissue measured, standard mass spectrometric analysis pipelines have proven inadequate. Here we describe how existing computational approaches can be adapted to focus on the specific biological questions asked in spatial proteomics experiments. We apply this approach to present an unbiased characterization of the human islet microenvironment comprising the entire complex array of cell types involved while maintaining spatial information and the degree of the islet’s sphere of influence. We identify specific functional activity unique to the pancreatic islet cells and demonstrate how far their signature can be detected in the adjacent tissue. Our results show that we can distinguish pancreatic islet cells from the neighboring exocrine tissue environment, recapitulate known biological functions of islet cells, and identify a spatial gradient in the expression of RNA processing proteins within the islet microenvironment. Graphical Abstract Highlights • microPOTS enables deep proteome imaging of pancreatic islets and their microenvironment.• We identified and quantified over 6000 proteins from ∼50,000 μm2 tissue area samples.• Differential expression and network analyses identified pathways uniquely active in islets.• Rank-based statistics enable the characterization of gradients across individual tissue images. In Brief We applied our Microdroplet Processing in One pot for Trace Samples (microPOTS) TMT platform to study the pancreatic islet microenvironment in the human pancreas. We were able to quantify over 6000 proteins from seven different regions within the same patient. Here we describe enhancements to existing computational approaches to extract functional hypotheses from this first-of-its-kind dataset. In addition to recapitulating known functions of the islet, we can identify specific immune and RNA processing activities with spatial heterogeneity in expression.

Dataset Information

Nestin expression in pancreatic endocrine and exocrine cells of mice lacking glucagon signaling.

Publications

Nestin expression in pancreatic endocrine and exocrine cells of mice lacking glucagon signaling.

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