The role of ATP-binding transporters associated with multi-drugresistance in stem cells

ATP-binding transporters (ABC-t) play various roles in regulation organism function and homeostasis from prokaryota to mammals. ABC-t mediate transport of mainly lipophilic substances through cellular membranes. Some ABC-t are important in cell protection against endogenous and importantly also exogenous toxins. These transporters are called ABC-t associated with multi-drug resistance (ABC-t/MDR), according to their role in resistance of tumor cells to pharmacotherapy. ABC-t/MDR are also over-expressed in stem cells, where their protective role is expected, too. Particularly, ABCB1, ABCC1, and ABCG2 are common ABC-t/MDR expressed in stem cells. However, substrates of ABC-t/MDR are not only toxins, but also important signaling molecules as well leukotrienes and/or glutathione conjugates and porphyrins, which mediated balance in intracellular oxidation-reduction processing. Thus we hypothesize the role of ABC-t/MDR also in regulation of stem cells fate. To test this hypothesis we analyzed effect of modulation of ABC-t/MDR activity in embryonic and neural stem cells. We observed that ABCC1 and ABCG2 are the most expressed ABC-t/MDR in our tested stem cells. Importantly, inhibition of these ABC-t/MDR leads to decreasing of stemness and induction of differentiation in both embryonic and neural stem cells. Analysis of mechanism of observed effect and identification of studying ABC-t/MDR substrates, which may be responsible for this effect, are in progression.