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

Life Sci Alliance. 2021 Jan 29;4(4):e202000840. doi: 10.26508/lsa.202000840. Print 2021 Apr.

Abstract

Highly sensitive approaches to target insulin-expressing cells would allow more effective imaging, sorting, and analysis of pancreatic β-cells. Here, we introduce the use of a reaction-based probe, diacetylated Zinpyr1 (DA-ZP1), to image pancreatic β-cells and β-like cells derived from human pluripotent stem cells. We harness the high intracellular zinc concentration of β-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 β-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 β-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Fluorescent Dyes / chemistry
  • Humans
  • Insulin-Secreting Cells / metabolism*
  • Islets of Langerhans / cytology
  • Islets of Langerhans / metabolism
  • Mice
  • Molecular Imaging / methods*
  • Molecular Probes* / chemistry
  • Molecular Structure

Substances

  • Fluorescent Dyes
  • Molecular Probes