Glycoprotein 2 is a specific cell surface marker of human pancreatic progenitors.
Glycoprotein 2 is a specific cell surface marker of human pancreatic progenitors.
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糖蛋白2是人类胰腺祖细胞的特定细胞表面标记。
DOI：
10.1038/s41467-017-00561-0
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发表时间：
2017-08-24
影响因子：
16.6
通讯作者：
Nostro MC
中科院分区：
文献类型：
--
作者：
Cogger KF;Sinha A;Sarangi F;McGaugh EC;Saunders D;Dorrell C;Mejia-Guerrero S;Aghazadeh Y;Rourke JL;Screaton RA;Grompe M;Streeter PR;Powers AC;Brissova M;Kislinger T;Nostro MC
PDX1+/NKX6-1+胰腺祖细胞（PPs）在体外和体内均可产生内分泌细胞。这种细胞群可以成功地从人类多能干细胞（hPSCs）中分化出来，并有可能产生无限供应的β细胞用于糖尿病治疗。然而，体外生成PP的效率是高度可变的，这对体外和体内研究的可重复性和有效性产生了负面影响，从而影响了向临床的转化。在这里，我们报告了使用蛋白质组学方法对hpsc衍生的PPs进行表型表征，并在分化过程中将这些细胞与非pp群体区分开来。我们的分析确定胰腺分泌颗粒膜主要糖蛋白2 （GP2）是pp特异性的细胞表面标记物。值得注意的是，GP2与NKX6-1和PTF1A在人类发育的胰腺中共表达，表明它在体内标记了多能性胰腺祖细胞。最后，我们发现分离的hpsc衍生的GP2+细胞比GP2 -和未分类的群体更有效地产生β样细胞（C-PEPTIDE+/NKX6-1+），强调了GP2潜在的治疗应用。胰腺祖细胞（PPs）可以在体外从人多能干细胞中获得，但分化效率存在差异，这给胰岛素生成细胞的分类带来了困难。在这里，作者使用蛋白质组学方法鉴定了分泌颗粒膜糖蛋白2作为PDX1+/NKX6-1+ PPs的标记物。
PDX1+/NKX6-1+ pancreatic progenitors (PPs) give rise to endocrine cells both in vitro and in vivo. This cell population can be successfully differentiated from human pluripotent stem cells (hPSCs) and hold the potential to generate an unlimited supply of β cells for diabetes treatment. However, the efficiency of PP generation in vitro is highly variable, negatively impacting reproducibility and validation of in vitro and in vivo studies, and consequently, translation to the clinic. Here, we report the use of a proteomics approach to phenotypically characterize hPSC-derived PPs and distinguish these cells from non-PP populations during differentiation. Our analysis identifies the pancreatic secretory granule membrane major glycoprotein 2 (GP2) as a PP-specific cell surface marker. Remarkably, GP2 is co-expressed with NKX6-1 and PTF1A in human developing pancreata, indicating that it marks the multipotent pancreatic progenitors in vivo. Finally, we show that isolated hPSC-derived GP2+ cells generate β-like cells (C-PEPTIDE+/NKX6-1+) more efficiently compared to GP2− and unsorted populations, underlining the potential therapeutic applications of GP2. Pancreatic progenitors (PPs) can be derived from human pluripotent stem cells in vitro but efficiency of differentiation varies, making it hard to sort for insulin-producing cells. Here, the authors use a proteomic approach to identify the secretory granule membrane glycoprotein 2 as a marker for PDX1+/NKX6-1+ PPs.
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影响因子：
21.3
作者：
通讯作者：
--
影响因子：
5.9
作者：
Nostro, M. Cristina;Sarangi, Farida;Yang, Chaoxing;Holland, Andrew;Elefanty, Andrew G.;Stanley, Edouard G.;Greiner, Dale L.;Keller, Gordon
通讯作者：
Keller, Gordon
DOI：
10.1016/j.bbrc.2013.12.070
发表时间：
2014-03-21
影响因子：
3.1
作者：
Sinha, Ankit;Ignatchenko, Vladimir;Kislinger, Thomas
通讯作者：
Kislinger, Thomas
影响因子：
6
作者：
Agulnick, Alan D.;Ambruzs, Dana M.;D'Amour, Kevin A.
通讯作者：
D'Amour, Kevin A.
影响因子：
1.2
作者：
Dorrell, Craig;Abraham, Stephanie L.;Grompe, Markus
通讯作者：
Grompe, Markus