A resource for discovering specific and universal biomarkers for distributed stem cells.

A resource for discovering specific and universal biomarkers for distributed stem cells.
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DOI:
10.1371/journal.pone.0022077
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Sherley JL
Sherley JL
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Noh M;Smith JL;Huh YH;Sherley JL

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分布式干细胞(DSC)的特异性和通用生物标志物一直难以捉摸。发现这种理想的DSC生物标志物的主要障碍是难以获得足够数量和纯度的DSC。为了解决这个问题,我们使用基因工程细胞系进行条件不对称自我更新,定义DSC属性。在基因芯片分析中,我们确定了85个基因的表达是紧密不对称自我更新相关(ASRA)。ASRA基因签名规定DSCs进行不对称自我更新的程度比定向祖细胞,胚胎干细胞或诱导多能干细胞更大。这种划分有几个重要的含义。其中包括:1)提供了实验证据,证明DSCs在体内作为个体细胞进行不对称自我更新; 2)解释了为什么早期试图定义DSCs的共同基因表达特征不成功; 3)预测一些ASRA蛋白可能是DSCs的理想生物标志物。事实上,两个ASRA蛋白,CXCR 6和BTG 2,和其他两个相关的自我更新模式相关的(SRPA)蛋白在这个基因资源,LGR 5和H2A.Z中确定,显示独特的不对称表达模式,具有普遍和特异性DSC鉴定的高潜力。
Specific and universal biomarkers for distributed stem cells (DSCs) have been elusive. A major barrier to discovery of such ideal DSC biomarkers is difficulty in obtaining DSCs in sufficient quantity and purity. To solve this problem, we used cell lines genetically engineered for conditional asymmetric self-renewal, the defining DSC property. In gene microarray analyses, we identified 85 genes whose expression is tightly asymmetric self-renewal associated (ASRA). The ASRA gene signature prescribed DSCs to undergo asymmetric self-renewal to a greater extent than committed progenitor cells, embryonic stem cells, or induced pluripotent stem cells. This delineation has several significant implications. These include: 1) providing experimental evidence that DSCs in vivo undergo asymmetric self-renewal as individual cells; 2) providing an explanation why earlier attempts to define a common gene expression signature for DSCs were unsuccessful; and 3) predicting that some ASRA proteins may be ideal biomarkers for DSCs. Indeed, two ASRA proteins, CXCR6 and BTG2, and two other related self-renewal pattern associated (SRPA) proteins identified in this gene resource, LGR5 and H2A.Z, display unique asymmetric patterns of expression that have a high potential for universal and specific DSC identification.
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