» Articles » PMID: 33514654

Harnessing Reaction-based Probes to Preferentially Target Pancreatic β-cells and β-like Cells

Overview
Date 2021 Jan 30
PMID 33514654
Citations 6
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

mA mRNA methylation by METTL14 regulates early pancreatic cell differentiation.

Kahraman S, De Jesus D, Wei J, Brown N, Zou Z, Hu J EMBO J. 2024; 43(22):5445-5468.

PMID: 39322760 PMC: 11574190. DOI: 10.1038/s44318-024-00213-2.


Zinc-chelating BET bromodomain inhibitors equally target islet endocrine cell types.

Jones Lipinski R, Stancill J, Nunez R, Wynia-Smith S, Sprague D, Nord J Am J Physiol Regul Integr Comp Physiol. 2024; 326(6):R515-R527.

PMID: 38618911 PMC: 11381023. DOI: 10.1152/ajpregu.00259.2023.


Fluorescein-based sensors to purify human α-cells for functional and transcriptomic analyses.

Kahraman S, Shibue K, De Jesus D, Kim H, Hu J, Manna D Elife. 2023; 12.

PMID: 37732504 PMC: 10567109. DOI: 10.7554/eLife.85056.


Excess pancreatic elastase alters acinar-β cell communication by impairing the mechano-signaling and the PAR2 pathways.

Basile G, Vetere A, Hu J, Ijaduola O, Zhang Y, Liu K Cell Metab. 2023; 35(7):1242-1260.e9.

PMID: 37339634 PMC: 10834355. DOI: 10.1016/j.cmet.2023.05.007.


Small-molecule discovery in the pancreatic beta cell.

Wagner B Curr Opin Chem Biol. 2022; 68:102150.

PMID: 35487100 PMC: 9188675. DOI: 10.1016/j.cbpa.2022.102150.


References
1.
Kahraman S, Okawa E, Kulkarni R . Is Transforming Stem Cells to Pancreatic Beta Cells Still the Holy Grail for Type 2 Diabetes?. Curr Diab Rep. 2016; 16(8):70. PMC: 5877461. DOI: 10.1007/s11892-016-0764-0. View

2.
Gamble A, Pepper A, Bruni A, Shapiro A . The journey of islet cell transplantation and future development. Islets. 2018; 10(2):80-94. PMC: 5895174. DOI: 10.1080/19382014.2018.1428511. View

3.
Kelly O, Chan M, Martinson L, Kadoya K, Ostertag T, Ross K . Cell-surface markers for the isolation of pancreatic cell types derived from human embryonic stem cells. Nat Biotechnol. 2011; 29(8):750-6. DOI: 10.1038/nbt.1931. View

4.
Que E, Domaille D, Chang C . Metals in neurobiology: probing their chemistry and biology with molecular imaging. Chem Rev. 2008; 108(5):1517-49. DOI: 10.1021/cr078203u. View

5.
Smith B, Akers W, Leevy W, Lampkins A, Xiao S, Wolter W . Optical imaging of mammary and prostate tumors in living animals using a synthetic near infrared zinc(II)-dipicolylamine probe for anionic cell surfaces. J Am Chem Soc. 2009; 132(1):67-9. PMC: 2805267. DOI: 10.1021/ja908467y. View