RESEARCH REPORT STEM CELLS AND REGENERATION

The differential activation of intracellular signaling pathways confers the permissiveness of embryonic stem cell derivation from different mouse strains Satoshi Ohtsuka1 and Hitoshi Niwa1,2,3,* The requirement of leukemia inhibitory factor (LIF) for theestablishment and maintenance of mouse embryonic stem cells (ESCs) depends on thegenetic backgroundof theESCorigin. To reveal themolecular basis of the strain-dependent function of LIF, we compared the activation of the intracellular signaling pathways downstream of LIF in ESCs with different genetic backgrounds. We found that the JAK-Stat3 pathway was dominantly activated in ESCs derived from ‘permissive ’ mouse strains (129Sv and C57BL6), whereas the MAP kinase pathway was hyperactivated in ESCs from ‘non-permissive ’ strains (NOD, CBA and FVB). Artificial activation of Stat3 supported stable self-renewal of ESCs from non-permissive strains. These data suggest that the difference in the balance between the two intracellular signaling pathways underlies the differential response to LIF