School of Pharmacy, Ajou University, Suwon, South Korea.
PLoS One. 2011;6(7):e22077. doi: 10.1371/journal.pone.0022077. Epub 2011 Jul 19.
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.
用于分散干细胞（DSC）的特异性和普遍性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，我们使用了经过基因工程改造的细胞系，用于条件性不对称自我更新，这是 DSC 的定义特性。在基因微阵列分析中，我们鉴定了 85 个基因，其表达与不对称自我更新密切相关（ASRA）。ASRA 基因特征规定 DSCs 比定向祖细胞、胚胎干细胞或诱导多能干细胞更能进行不对称自我更新。这一描绘具有几个重要意义。这些包括：1）提供实验证据，证明体内 DSCs 作为单个细胞进行不对称自我更新；2）解释为什么早期尝试定义 DSC 的共同基因表达特征不成功；3）预测某些 ASRA 蛋白可能是 DSC 的理想生物标志物。事实上，两种 ASRA 蛋白，CXCR6 和 BTG2，以及在这个基因资源中鉴定的另外两种相关的自我更新模式相关（SRPA）蛋白，LGR5 和 H2A.Z，显示出独特的不对称表达模式，具有普遍和特异性 DSC 识别的高潜力。
