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ACS Chem Biol. 2016 Sep 16;11(9):2588-95. doi: 10.1021/acschembio.6b00602. Epub 2016 Jul 29.

Single Cell Peptide Heterogeneity of Rat Islets of Langerhans.

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Department of Chemistry and the Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.


Measuring the chemical composition of individual cells in mammalian organs can provide critical insights toward understanding the mechanisms leading to their normal and pathological function. In this work, single cell heterogeneity of islets of Langerhans is characterized with high throughput by microscopy-guided single cell matrix-assisted laser desorption/ionization mass spectrometry. Two levels of chemical heterogeneity were observed from the analysis of more than 3000 individual cells. Within a single islet, cellular heterogeneity was evident from the exclusive expression of the canonical biomarkers glucagon, insulin, pancreatic polypeptide (PP), and somatostatin within α-, β-, γ-, and δ-cells, respectively. We localized the neuropeptide WE-14, a known cell-to-cell signaling molecule, to individual δ-cells. Moreover, several unreported endogenous peptides generated by dibasic site cleavages of PP were detected within individual γ-cells. Of these, PP(27-36) was previously shown to activate the human Y4 receptor, suggesting it has a signaling role in vivo. Heterogeneity in cell composition was also observed between islets as evidenced by a 50-fold larger α-cell population in islets of the dorsal pancreas compared to the ventral-derived pancreatic islets. Finally, PP(27-36) was more abundant in γ-cells from the ventral region of the pancreas, indicating differences in the extent of PP-prohormone processing in the two regions of the pancreas.

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