Tan Shen Mynn, Wang Siew Tein, Hentze Hannes, Dröge Peter
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 and ES Cell International Pte Ltd, 11 Biopolis Way, #05-06 Helios, 138667 Singapore.
Nucleic Acids Res. 2007;35(18):e118. doi: 10.1093/nar/gkm704. Epub 2007 Sep 12.
Undifferentiated transcription factor 1 (UTF1) was identified first in mouse embryonic stem cells and is also expressed in human embryonic and adult stem cells. UTF1 transcription ceases at the onset of differentiation, which clearly distinguishes it from less sensitive pluripotency markers, such as Oct4 or Nanog. We present here two transgenic hESC lines, named ZUN. Each line harbors one copy of the UTF1 promoter/enhancer driving a resistance gene and yielded highly homogeneous cultures under selection pressure, with a larger proportion of Oct4 and Sox2 positive cells. While ZUN cultures, like parental HUES8 cultures, retained the capacity to differentiate into tissues of all three germ layers using a SICD mouse teratoma model, they surprisingly exhibited an increased refractoriness to various differentiation cues in vitro. Together with its small size of only 2.4 kb for the entire cassette, these features render our selection system a powerful novel tool for many stem cell applications and human somatic cell reprogramming strategies.
未分化转录因子1（UTF1）最早在小鼠胚胎干细胞中被发现，在人类胚胎干细胞和成人干细胞中也有表达。UTF1转录在分化开始时停止，这使其与Oct4或Nanog等敏感性较低的多能性标志物明显区分开来。我们在此展示了两个转基因人胚胎干细胞系，命名为ZUN。每个细胞系都含有一个驱动抗性基因的UTF1启动子/增强子拷贝，并在选择压力下产生了高度均一的培养物，其中Oct4和Sox2阳性细胞的比例更高。虽然ZUN培养物与亲本HUES8培养物一样，使用SICD小鼠畸胎瘤模型保留了分化为所有三个胚层组织的能力，但令人惊讶的是，它们在体外对各种分化信号的耐受性增强。连同其整个盒式结构仅2.4 kb的小尺寸，这些特性使我们的选择系统成为许多干细胞应用和人类体细胞重编程策略的强大新型工具。
