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

View ORCID ProfileSevim Kahraman, Debasish Manna, View ORCID ProfileErcument Dirice, Basudeb Maji, Jonnell Small, View ORCID ProfileBridget K Wagner, View ORCID ProfileAmit Choudhary  Correspondence email, View ORCID ProfileRohit N Kulkarni  Correspondence email
Sevim Kahraman
1Islet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Brigham and Women’s Hospital, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA
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  • ORCID record for Sevim Kahraman
Debasish Manna
2Chemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
3Department of Medicine, Harvard Medical School, Boston, MA, USA
4Divisions of Renal Medicine and Engineering, Brigham and Women’s Hospital, Boston, MA, USA
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Ercument Dirice
1Islet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Brigham and Women’s Hospital, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA
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Basudeb Maji
2Chemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
3Department of Medicine, Harvard Medical School, Boston, MA, USA
4Divisions of Renal Medicine and Engineering, Brigham and Women’s Hospital, Boston, MA, USA
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Jonnell Small
2Chemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
5Chemical Biology Program, Harvard University, Cambridge, MA, USA
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Bridget K Wagner
2Chemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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  • ORCID record for Bridget K Wagner
Amit Choudhary
2Chemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
3Department of Medicine, Harvard Medical School, Boston, MA, USA
4Divisions of Renal Medicine and Engineering, Brigham and Women’s Hospital, Boston, MA, USA
5Chemical Biology Program, Harvard University, Cambridge, MA, USA
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  • For correspondence: achoudhary@bwh.harvard.edu
Rohit N Kulkarni
1Islet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Brigham and Women’s Hospital, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA
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  • ORCID record for Rohit N Kulkarni
  • For correspondence: Rohit.Kulkarni@joslin.harvard.edu
Published 29 January 2021. DOI: 10.26508/lsa.202000840
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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.

  • Received July 5, 2020.
  • Revision received January 11, 2021.
  • Accepted January 12, 2021.
  • © 2021 Kahraman et al.
Creative Commons logoCreative Commons logohttps://creativecommons.org/licenses/by/4.0/

This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).

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Developing approaches to target β-cells
Sevim Kahraman, Debasish Manna, Ercument Dirice, Basudeb Maji, Jonnell Small, Bridget K Wagner, Amit Choudhary, Rohit N Kulkarni
Life Science Alliance Jan 2021, 4 (4) e202000840; DOI: 10.26508/lsa.202000840

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Developing approaches to target β-cells
Sevim Kahraman, Debasish Manna, Ercument Dirice, Basudeb Maji, Jonnell Small, Bridget K Wagner, Amit Choudhary, Rohit N Kulkarni
Life Science Alliance Jan 2021, 4 (4) e202000840; DOI: 10.26508/lsa.202000840
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Volume 4, No. 4
April 2021
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