UC San Diego

Mouse embryonic stem cells (mESCs) are the in vitro counterpart of the epiblast, possessing the ability to self-renew and differentiate into all cell types of the organism. mESC pluripotency and loss thereof is controlled by an immense regulatory network of factors, for which both post-transcriptional and epigenetic regulation play important roles. To investigate thepotential role of the cytoplasmic RNA binding protein and decay activator ZFP36L2 in this context, I generated mESCs lacking ZFP36L2 expression using the Cre-loxP system. Together, this is a powerful cell system, which allows Zfp36l2 to be knocked out at different points of cell differentiation in vitro. To facilitate the detection of KO cells, the lines I created also included the mTmG double reporter that can be used to easily monitor and sort for cells after Cre recombination. Using this system in mESCs, I discovered that knockout of ZFP36L2 potentially acts to reinforce pluripotency and 2-cell-like conversion. I also found that ZFP36L2 may also be necessary for normal differentiation, as knockout leads to aberrant expression of mesendoderm markers. Together, these data point to a potential novel role for RNA decay by ZFP36L2 as a repressor of pluripotency and regulator of germ layer specification.