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.
Cell Metab. 2019 Mar 5;29(3):745-754.e4. doi: 10.1016/j.cmet.2018.10.007. Epub 2018 Nov 15.
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.
鉴定人胰腺β细胞表面的特异性标志物将允许进行体内分析和成像。在这里，我们引入了一种生物标志物，即核苷酸三磷酸二磷酸水解酶-3（NTPDase3），它表达在几乎所有成年人类β细胞的细胞表面，包括 1 型或 2 型糖尿病患者的β细胞。NTPDase3 在人胰腺发育的产后阶段动态表达，出生时首先在腺泡细胞中出现，但几个月后，其在腺泡细胞中的表达下降，而同时在胰岛β细胞中出现。鉴于其特异性和膜定位，我们利用 NTPDase3 抗体对活的人β细胞进行纯化，正如转录谱所证实的那样，并且还用于移植的人β细胞的体内成像。因此，NTPDase3 是人成年β细胞的表面标志物，针对该蛋白的抗体应该是用于β细胞分选、体内成像和靶向的有用新试剂。
