ZIGIR, a Granule-Specific Zn2+ Indicator, Reveals Human Islet α Cell Heterogeneity.

Cell Reports
Ebrahim H Ghazvini ZadehWen-Hong Li

Abstract

Numerous mammalian cells contain abundant Zn2+ in their secretory granules, yet available Zn2+ sensors lack the desired specificity and sensitivity for imaging granular Zn2+. We developed a fluorescent zinc granule indicator, ZIGIR, that possesses numerous desired properties for live cell imaging, including >100-fold fluorescence enhancement, membrane permeability, and selective enrichment to acidic granules. The combined advantages endow ZIGIR with superior sensitivity and specificity for imaging granular Zn2+. ZIGIR enables separation of heterogenous β cells based on their insulin content and sorting of mouse islets into pure α cells and β cells. In human islets, ZIGIR facilitates sorting of endocrine cells into highly enriched α cells and β cells, reveals unexpectedly high Zn2+ activity in the somatostatin granule of some δ cells, and uncovers variation in the glucagon content among human α cells. We expect broad applications of ZIGIR for studying Zn2+ biology and Zn2+-rich secretory granules and for engineering β cells with high insulin content for treating diabetes.

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Citations

Sep 30, 2020·Pharmaceuticals·Pooyan KhalighinejadA Dean Sherry
Nov 4, 2020·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Su-Tang LoA Dean Sherry
Mar 6, 2021·Molecular and Cellular Biochemistry·Carla P Barragán-ÁlvarezNestor E Díaz-Martínez
Mar 27, 2021·Frontiers in Endocrinology·Shiuhwei ChenWen-Hong Li
May 1, 2021·International Journal of Molecular Sciences·Petra I LorenzoBenoit R Gauthier
Mar 6, 2021·Immunology and Cell Biology·Pascal de Boer, Ben Ng Giepmans

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