ABC transporters confer multidrug resistance to Drosophila intestinal stem cells

Dayton, H.; DiRusso, J.; Kolbert, K.; Williamson, O.; Balciunaite, A.; D'Souza, E.; Becker, K.; Hosage, E.; Issa, M.; Liu, V.; Viswanatha, R.; Kondo, S.; Markstein, M.

doi:10.1101/511584

bioRxiv · 10.1101/511584

ABC transporters confer multidrug resistance to Drosophila intestinal stem cells

Dayton, H.·DiRusso, J.·Kolbert, K.·Williamson, O.·Balciunaite, A.·D'Souza, E.·Becker, K.·Hosage, E.·Issa, M.·Liu, V.·Viswanatha, R.·Kondo, S.·Markstein, M.

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Abstract

Adult stem cells can survive a wide variety of insults from ionizing radiation to toxic chemicals1-3. To date, the multidrug resistant features of stem cells have been characterized only in vertebrates, where there is a critical need to understand how cancer stem cells thwart chemotherapy drugs4-6. These studies reveal that the ability of both normal and cancer stem cells to survive toxins hinges on their high levels of expression of ABC transporters, transmembrane pumps that efflux lipophilic compounds out of cells7,8. This has been observed across a wide spectrum of vertebrate stem cells including breast, blood, intestine, liver, and skin, suggesting that high efflux ability and multidrug resistance may be general features of stem cells that distinguish them from their differentiated daughter cells. Here we show that these previously described vertebrate stem cell features are conserved in Drosophila intestinal stem cells. Using a novel in vivo efflux assay and multiple drug challenges, we show that stem cells in the fly intestine depend on two ABC transporters--one constitutively expressed and the other induced--for efflux and multidrug resistance. These results suggest that stem cell multidrug resistance by ABC transporters is a general stem cell feature conserved over 500 million years of evolution.

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Dayton, H., DiRusso, J., Kolbert, K., Williamson, O., Balciunaite, A., D'Souza, E., Becker, K., Hosage, E., Issa, M., Liu, V., Viswanatha, R., Kondo, S., Markstein, M.. 2019-01-04. ABC transporters confer multidrug resistance to Drosophila intestinal stem cells. https://doi.org/10.1101/511584

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