ZIGIR, a Granule-Specific Zn2+ Indicator, Reveals Human Islet α Cell Heterogeneity.
Cell Rep
; 32(2): 107904, 2020 07 14.
Article
em En
| MEDLINE
| ID: mdl-32668245
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 ß cells based on their insulin content and sorting of mouse islets into pure α cells and ß cells. In human islets, ZIGIR facilitates sorting of endocrine cells into highly enriched α cells and ß 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 ß cells with high insulin content for treating diabetes.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Zinco
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Ilhotas Pancreáticas
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Grânulos Citoplasmáticos
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Células Secretoras de Glucagon
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Corantes Fluorescentes
Limite:
Adult
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Aged
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article