Dataset Information

BMP-7 Induces Adult Human Pancreatic Exocrine-to-Endocrine Conversion.

ABSTRACT: The exocrine pancreas can give rise to endocrine insulin-producing cells upon ectopic expression of key transcription factors. However, the need for genetic manipulation remains a translational hurdle for diabetes therapy. Here we report the conversion of adult human nonendocrine pancreatic tissue into endocrine cell types by exposure to bone morphogenetic protein 7. The use of this U.S. Food and Drug Administration-approved agent, without any genetic manipulation, results in the neogenesis of clusters that exhibit high insulin content and glucose responsiveness both in vitro and in vivo. In vitro lineage tracing confirmed that BMP-7-induced insulin-expressing cells arise mainly from extrainsular PDX-1(+), carbonic anhydrase II(-) (mature ductal), elastase 3a (acinar)(-) , and insulin(-) subpopulations. The nongenetic conversion of human pancreatic exocrine cells to endocrine cells is novel and represents a safer and simpler alternative to genetic reprogramming.

SUBMITTER: Klein D

PROVIDER: S-EPMC4657585 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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BMP-7 Induces Adult Human Pancreatic Exocrine-to-Endocrine Conversion.

Klein Dagmar D Álvarez-Cubela Silvia S Lanzoni Giacomo G Vargas Nancy N Prabakar Kamalaveni R KR Boulina Maria M Ricordi Camillo C Inverardi Luca L Pastori Ricardo L RL Domínguez-Bendala Juan J

Diabetes 20150825 12

The exocrine pancreas can give rise to endocrine insulin-producing cells upon ectopic expression of key transcription factors. However, the need for genetic manipulation remains a translational hurdle for diabetes therapy. Here we report the conversion of adult human nonendocrine pancreatic tissue into endocrine cell types by exposure to bone morphogenetic protein 7. The use of this U.S. Food and Drug Administration-approved agent, without any genetic manipulation, results in the neogenesis of c ...[more]

PMID: 26307584

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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

BMP-7 Induces Adult Human Pancreatic Exocrine-to-Endocrine Conversion.

Publications

BMP-7 Induces Adult Human Pancreatic Exocrine-to-Endocrine Conversion.

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