Cell cycle regulators control the stem cell self-renewal and determine the cell fates, miRNAs may regulate G1/S transition in stem cell division. Using the Drosophila germline stem cells (GSC) as a model, Hatfield et al. specifically inactivate the Dicer-1, which is required for miRNA pathway. They found that the rate of cell division in dcr-1 mutant GSCs was decreased. The cell cycle markers Cyclin E is high expressed, and the S phase is reduced. These studies indicate that perturbation of the miRNA pathway by mutant dcr-1 in GSCs delays the cell cycle at the G/S transition. Their studies further documented that miRNA may bind to 3'UTR of Daccpo gene (a homologue of the p21/p27 family of cyclin-dependent kinase inhibitors) and inhibit its activity; consequently, activate the Cyclin E protein . Murchison et al [33] recently generated Dicer deficient (exon 18, 22-23 in dicer gene) mouse ES cells ( DCR ), they observed these DCR mouse ES cells exhibit a significant proliferative defect comparing to wild type or heterozygomous ES cells. This phenotype change is consistent with other dicer knockout (exons 18-20) mouse ES cells (DCRa,a ES) [34]. Moreover, the DCR- - ES cells altered cell cycle profile which increase in Gi and G0 cells and a corresponding decrease of cells in G2 and M phase.

Collectively, specific miRNAs turn on or off the gate of cell cycle, which regulate the stem cells fate under physiological conditions (Figure 2).

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