Harnessing reaction-based probes to preferentially target pancreatic β-cells and β-like cells

Highly sensitive approaches to target insulin-expressing cells would allow more effective imaging, sorting, and analysis of pancreatic beta-cells. Here, we introduce the use of a reaction-based probe, diacetylated Zinpyr1 (DA-ZP1), to image pancreatic beta-cells and beta-like cells derived from human pluripotent stem cells. We harness the high intracellular zinc concentration of beta-cells to induce a fluorescence signal in cells after administration of DA-ZP1. Given its specificity and rapid uptake by cells, we used DA-ZP1 to purify live stem cell-derived beta-like cells as confirmed by immunostaining analysis. We tested the ability of DA-ZP1 to image transplanted human islet grafts and endogenous mouse pancreatic islets in vivo after its systemic administration into mice. Thus, DA-ZP1 enables purification of insulin-secreting beta-like cells for downstream applications, such as functional studies, gene-expression, and cell-cell interaction analyses and can be used to label engrafted human islets and endogenous mouse islets in vivo.

Automated summary

The reaction-based probe DA-ZP1 provides a sensitive method for imaging and purifying insulin-expressing cells like pancreatic beta-cells, derived from human pluripotent stem cells. It can be used for downstream applications such as functional studies, gene-expression, and cell-cell interaction analyses. Additionally, DA-ZP1 is capable of labeling engrafted human islets and endogenous mouse islets in vivo.