[医学]miRNAs and stem cells.pptVIP

GENES DEVELOPMENT 24:2732–2741 2010 miRNAs Regulate the G1/S Transition in Mouse Embryonic Stem Cells The proliferation rate of mouse ES cells is extremely fast with a cycling time of ~10 h. The length of cycling time is increased to more than 18 h in differentiated cells. ES cells have an unusually short G1 phase (~2 h) with most (~70%) cells in S phase. ES cells lack a G1 restriction point or checkpoint, therefore can proliferate even in the absence of growth factors or mitogens. In mouse ES cells, the Cdk4/Cdk6–Cyclin D complex is not present or active, while the Cdk+2–Cyclin E complex is constitutively active throughout the cell cycle. During differentiation, the Cdk2–Cyclin E activity is decreased and becomes cell cycle dependent Cdks: cyclin-dependent kinases G1期PCC为单线状，因DNA未复制。 S期PCC为粉末状，因DNA由多个部位开始复制。 G2期PCC为双线染色体，说明DNA复制已完成。 细胞生长周期 Cdks: cyclin-dependent kinases 细胞周期蛋白依赖性激酶 激活的CDK1可将靶蛋白磷酸化而产生相应的生理效应，如将核纤层蛋白磷酸化导致核纤层解体、核膜消失，将H1磷酸化导致染色体的凝缩等等。这些效应的最终结果是细胞周期的不断运行。因此，CDK激酶和其调节因子又被称作细胞周期引擎。 A) mESCs exhibit high mir-290 miRNA levels and elevated Cdk2-cyclin E activity, leading to accelerated G1-S progression and a corresponding short G1 phase. mir-290 inhibits the accumulation of p21Cip1, allowing unrestrained Cdk2-cyclin E activity. (B) As mir-290 miRNAs are down- regulated during differentiation, or in cells deficient for Dcgr3, p21Cip1 accumulates and assembles into complexes that inactivate Cdk2-cyclin E. The diminished cdk activity is thought to delay rogression from G1 into S phase, thus lengthening overall generation times. mir-290 miRNA Regulation of G1 Progression in mESCs Cell cycle profiles of ES cells, differentiated ES cells, and miRNA-deficient ES cells. More cells accumulate in G1 phase in differentiated cells and miRNA deficient ES cells than undifferentiated ES cells. Screening strategy to identify cell cycle-regulating miRNAs in miRNA-deficient ES cell model ESCC miRNAs promote the G1/S transition in ES cells by repressing multiple in