Abstract
RNA interference-mediated suppression of DICER and DROSHA in human embryonic stem cells (hESCs) attenuates cell proliferation, supporting a role for an intact microRNA (miRNA) pathway in the control of hESC cell division. Normal cell growth can be partially restored by introduction of the mature miRNAs miR-195 and miR-372. These miRNAs regulate two tumor suppressor genes, respectively: WEE1, which encodes a negative G2/M kinase modulator of the cycB/CDK complex and CDKN1A, which encodes p21, a cycE/CDK cyclin dependent kinase inhibitor that regulates the G1/S transition. We show that in wild-type hESCs, WEE1 levels control the rate of hESC division, whereas p21 levels must be maintained at a low level for hESC division to proceed. These data support a model for hESC cell cycle control in which miRNAs regulate negative cell cycle modulators at two phases of the cell cycle to ensure proper replenishment of the stem cell population.Supplemental information can be found here.
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