Dev111104 31..40

The maintenance and control of pluripotency is of great interest in stem cell biology. The dual specificity T-box/basic-helix-loop-helix-zipper transcription factor Mga is expressed in the pluripotent cells of the inner cell mass (ICM) and epiblast of the peri-implantation mouse embryo, but its function has not been investigated previously. Here, we use a loss-of-function allele and RNA knockdown to demonstrate that Mga depletion leads to the death of proliferating pluripotent ICM cells in vivo and in vitro, and the death of embryonic stem cells (ESCs) in vitro. Additionally, quiescent pluripotent cells lacking Mga are lost during embryonicdiapause.ExpressionofOdc1, the rate-limitingenzyme in the conversion of ornithine into putrescine in the synthesis of polyamines, is reduced inMgamutant cells, and the survival ofmutant ICMcells aswell as ESCs is rescued in culture by the addition of exogenous putrescine. These results suggestamechanismwherebyMga influencespluripotent cell survival through regulation of the polyamine pool in pluripotent cells of the embryo, whether they are in a proliferative or quiescent state.