Nature报道胚胎干细胞研究新进展

德克萨斯大学的科研小组最近在国际顶级杂志Nature上发表了题为"REST maintains self-renewal and pluripotency of embryonic stem cells"论文。科研人员发现REST (RE1-silencing transcription factor)可通过抑制microRNA miR-21表达，来维持小鼠胚胎干细胞的自我更新以及多能性。该研究中高可靠性的microRNA表达谱分析是由美国LC Sciences公司参与完成。

LC Sciences将创新的µParaflo^®技术和专利探针设计技术应用于微阵列检测平台，不仅可对全基因组microRNA表达谱进行检测，同时还确保了对microRNA进行直接的高灵敏和高特异的检测。LC Sciences提供的microRNA微阵列芯片检测服务可对Sanger miRBase数据库最新报道(11.0版, 2008/4)的包括人、大鼠、小鼠、哺乳动物、鱼类、植物、微生物、病毒等在内的所有单个物种或是同类物种microRNA序列进行检测分析。

点击了解更多信息

REST maintains self-renewal and pluripotency of embryonic stem cells

Singh SK, Kagalwala MN, Parker-Thornburg J, Adams H, Majumder S.

Department of Cancer Genetics, Center for Stem Cell and Developmental Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA

The neuronal repressor REST (RE1-silencing transcription factor; also called NRSF) is expressed at high levels in mouse embryonic stem (ES) cells, but its role in these cells is unclear. Here we show that REST maintains self-renewal and pluripotency in mouse ES cells through suppression of the microRNA miR-21. We found that, as with known self-renewal markers, the level of REST expression is much higher in self-renewing mouse ES cells than in differentiating mouse ES (embryoid body, EB) cells. Heterozygous deletion of Rest (Rest(+/-)) and its short-interfering-RNA-mediated knockdown in mouse ES cells cause a loss of self-renewal-even when these cells are grown under self-renewal conditions-and lead to the expression of markers specific for multiple lineages. Conversely, exogenously added REST maintains self-renewal in mouse EB cells. Furthermore, Rest(+/-) mouse ES cells cultured under self-renewal conditions express substantially reduced levels of several self-renewal regulators, including Oct4 (also called Pou5f1), Nanog, Sox2 and c-Myc, and exogenously added REST in mouse EB cells maintains the self-renewal phenotypes and expression of these self-renewal regulators. We also show that in mouse ES cells, REST is bound to the gene chromatin of a set of miRNAs that potentially target self-renewal genes. Whereas mouse ES cells and mouse EB cells containing exogenously added REST express lower levels of these miRNAs, EB cells, Rest(+/-) ES cells and ES cells treated with short interfering RNA targeting Rest express higher levels of these miRNAs. At least one of these REST-regulated miRNAs, miR-21, specifically suppresses the self-renewal of mouse ES cells, corresponding to the decreased expression of Oct4, Nanog, Sox2 and c-Myc. Thus, REST is a newly discovered element of the interconnected regulatory network that maintains the self-renewal and pluripotency of mouse ES cells.