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Cell Metab. 2018 Nov 12. pii: S1550-4131(18)30639-9. doi: 10.1016/j.cmet.2018.10.007. [Epub ahead of print]

Ectonucleoside Triphosphate Diphosphohydrolase-3 Antibody Targets Adult Human Pancreatic β Cells for In Vitro and In Vivo Analysis.

Author information

1
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37240, USA.
2
Department of Medicine, Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
3
HudsonAlpha Institute of Biotechnology, Huntsville, AL 35806, USA.
4
Flow Cytometry Shared Resource, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
5
Centre de recherche du CHU de Québec - Université Laval, Québec City, QC G1V 4G2, Canada.
6
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
7
Department of Diagnostic Medicine, Dell Medical School, University of Texas at Austin, Austin, TX 78712, USA.
8
Department of Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA 01655, USA.
9
The Jackson Laboratory, Bar Harbor, ME 04609, USA.
10
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37232, USA.
11
Centre de recherche du CHU de Québec - Université Laval, Québec City, QC G1V 4G2, Canada; Départment de Microbiologie-Infectiologie et d'Immunologie, Faculté de Médecine, Université Laval, Québec City, QC G1V 0A6, Canada.
12
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37240, USA; Department of Medicine, Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, TN 37232, USA; VA Tennessee Valley Healthcare, Nashville, TN 37212, USA. Electronic address: al.powers@vanderbilt.edu.

Abstract

Identification of cell-surface markers specific to human pancreatic β cells would allow in vivo analysis and imaging. Here we introduce a biomarker, ectonucleoside triphosphate diphosphohydrolase-3 (NTPDase3), that is expressed on the cell surface of essentially all adult human β cells, including those from individuals with type 1 or type 2 diabetes. NTPDase3 is expressed dynamically during postnatal human pancreas development, appearing first in acinar cells at birth, but several months later its expression declines in acinar cells while concurrently emerging in islet β cells. Given its specificity and membrane localization, we utilized an NTPDase3 antibody for purification of live human β cells as confirmed by transcriptional profiling, and, in addition, for in vivo imaging of transplanted human β cells. Thus, NTPDase3 is a cell-surface biomarker of adult human β cells, and the antibody directed to this protein should be a useful new reagent for β cell sorting, in vivo imaging, and targeting.

KEYWORDS:

development; diabetes; glucagon; imaging; insulin; islet; pancreas

PMID:
30449685
DOI:
10.1016/j.cmet.2018.10.007

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