胚胎干细胞分化中Rex1（zfp42）功能的分析。
Analysis of Rex1 (zfp42) function in embryonic stem cell differentiation.
作者信息
Scotland Kymora B, Chen Siming, Sylvester Renia, Gudas Lorraine J
机构信息
Department of Pharmacology, Weill Medical College of Cornell University, New York, New York 10065, USA.
出版信息
Dev Dyn. 2009 Aug;238(8):1863-77. doi: 10.1002/dvdy.22037.
Abstract
Rex1 (zfp42) is a zinc finger protein expressed primarily in undifferentiated stem cells, both in the embryo and the adult. Upon all-trans retinoic acid induced differentiation of murine embryonic stem (ES) cells, Rex1 mRNA levels decrease several fold. To characterize the function(s) of Rex1 more extensively, we generated Rex1 double knockout ES cell lines. The disruption of the Rex1 gene enhanced the expression of ectoderm, mesoderm, and endoderm markers as compared to wild-type (Wt) cells. We propose that Rex1 acts to reduce retinoic acid induced differentiation in ES cells. We performed microarray analyses on Wt and Rex1-/- cells cultured in the presence or absence of LIF to identify potential Rex1 targets. We also evaluated gene expression in a Wt line that overexpresses Rex1 and in a Rex1-/- line in which Rex1 expression was restored. These data, taken together, suggest that Rex1 influences differentiation, cell cycle regulation, and cancer progression.
摘要
Rex1（zfp42）是一种锌指蛋白，主要在胚胎和成体的未分化干细胞中表达。在全反式视黄酸诱导小鼠胚胎干细胞（ES细胞）分化时，Rex1 mRNA水平下降数倍。为了更全面地表征Rex1的功能，我们构建了Rex1双敲除ES细胞系。与野生型（Wt）细胞相比，Rex1基因的破坏增强了外胚层、中胚层和内胚层标志物的表达。我们提出，Rex1在ES细胞中起到减少视黄酸诱导分化的作用。我们对在有或无白血病抑制因子（LIF）的情况下培养的Wt和Rex1-/-细胞进行了微阵列分析，以鉴定潜在的Rex1靶点。我们还评估了过表达Rex1的Wt细胞系和恢复Rex1表达的Rex1-/-细胞系中的基因表达。综合这些数据表明，Rex1影响分化、细胞周期调控和癌症进展。
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