TeratoScore: Assessing the Differentiation Potential of Human Pluripotent Stem Cells by Quantitative Expression Analysis of Teratomas.

TeratoScore: Assessing the Differentiation Potential of Human Pluripotent Stem Cells by Quantitative Expression Analysis of Teratomas.
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DOI:
10.1016/j.stemcr.2015.05.006
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发表时间:
2015-06-09
期刊:
影响因子:
5.9
通讯作者:
Benvenisty, Nissim
Benvenisty, Nissim
中科院分区:
医学1区
文献类型:
--
作者:
Avior, Yishai;Biancotti, Juan Carlos;Benvenisty, Nissim

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畸胎瘤形成是测试人类多能干细胞分化成所有胚胎胚层能力的金标准试验。虽然广泛使用,但很少有人努力将这种定性分析转化为定量分析。利用来自多种细胞的基因表达数据,我们创建了一个记分卡,代表来自所有胚层和胚胎外组织的组织。TeratoScore是一个基于该记分卡的在线开源平台,它将多能干细胞衍生的畸胎瘤与恶性肿瘤区分开来,将细胞效力转化为定量测量(http://benvenisty.huji.ac.il/teratoscore.php)。用于该算法的畸胎瘤也允许我们检查具有二倍体核型的肿瘤和由非整倍体细胞发起的肿瘤之间的基因表达差异。染色体异常畸胎瘤表现出与起源于二倍体细胞的畸胎瘤明显不同的基因表达特征,特别是中枢神经系统特异性基因,与人类染色体综合征一致。一个代表所有生殖层的人类组织的基因记分卡被创建,一个名为TeratoScore的定量多能性测试是基于这个记分卡TeratoScore区分多能干细胞衍生的畸胎瘤和其他肿瘤来自非整倍体细胞的畸胎瘤显示异常的组织表达分布畸胎瘤形成是定义细胞多能性的金标准试验。在本文中,Benvenisty及其同事利用全局基因表达分析将该检测的定性特征转化为定量特征,取代了多能性的组织学评估。此外,他们发现畸胎瘤起源于非整倍体细胞,表现出异常的组织表达分布,这是畸胎瘤发育缺陷的特征。
Teratoma formation is the gold standard assay for testing the capacity of human pluripotent stem cells to differentiate into all embryonic germ layers. Although widely used, little effort has been made to transform this qualitative assay into a quantitative one. Using gene expression data from a wide variety of cells, we created a scorecard representing tissues from all germ layers and extraembryonic tissues. TeratoScore, an online, open-source platform based on this scorecard, distinguishes pluripotent stem cell-derived teratomas from malignant tumors, translating cell potency into a quantitative measure (http://benvenisty.huji.ac.il/teratoscore.php). The teratomas used for the algorithm also allowed us to examine gene expression differences between tumors with a diploid karyotype and those initiated by aneuploid cells. Chromosomally aberrant teratomas show a significantly different gene expression signature from that of teratomas originating from diploid cells, particularly in central nervous system-specific genes, congruent with human chromosomal syndromes. A gene scorecard representing human tissues from all germ layers was created A quantitative pluripotency test named TeratoScore was based on this scorecard TeratoScore distinguishes pluripotent stem cell-derived teratomas from other tumors Teratomas derived from aneuploid cells show aberrant tissue expression distribution Teratoma formation is a gold standard assay when defining pluripotency of cells. In this paper, Benvenisty and colleagues utilized global gene expression analysis to transform the qualitative character of this assay into a quantitative one, replacing histological assessment of pluripotent capabilities. Moreover, they show that teratomas initiated from aneuploid cells show an aberrant tissue expression distribution, characteristic of their developmental defects.
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期刊: STEM CELLS
影响因子: 5.2
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