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ABC transporters confer multidrug resistance to Drosophila intestinal stem cells

Hannah Dayton, Jonathan DiRusso, Kristopher Kolbert, Olivia Williamson, Aiste Balciunaite, Edridge D’Souza, Kelly Becker, Elizaveta Hosage, Muneera Issa, Victoria Liu, Raghuvir Viswanatha, Shu Kondo, Michele Markstein
doi: https://doi.org/10.1101/511584
Hannah Dayton
2Biology Department, University of Massachusetts Amherst, 611 North Pleasant Street, Amherst MA 01003
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Jonathan DiRusso
2Biology Department, University of Massachusetts Amherst, 611 North Pleasant Street, Amherst MA 01003
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Kristopher Kolbert
2Biology Department, University of Massachusetts Amherst, 611 North Pleasant Street, Amherst MA 01003
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Olivia Williamson
2Biology Department, University of Massachusetts Amherst, 611 North Pleasant Street, Amherst MA 01003
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Aiste Balciunaite
2Biology Department, University of Massachusetts Amherst, 611 North Pleasant Street, Amherst MA 01003
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Edridge D’Souza
2Biology Department, University of Massachusetts Amherst, 611 North Pleasant Street, Amherst MA 01003
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Kelly Becker
2Biology Department, University of Massachusetts Amherst, 611 North Pleasant Street, Amherst MA 01003
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Elizaveta Hosage
2Biology Department, University of Massachusetts Amherst, 611 North Pleasant Street, Amherst MA 01003
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Muneera Issa
2Biology Department, University of Massachusetts Amherst, 611 North Pleasant Street, Amherst MA 01003
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Victoria Liu
2Biology Department, University of Massachusetts Amherst, 611 North Pleasant Street, Amherst MA 01003
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Raghuvir Viswanatha
3Gentics Department, Harvard Medical School, 77 Avenue Louis Pasteur, Boston MA 02115
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Shu Kondo
4Genetic Strains Research Center, National Institute of Genetics, Mishima, Japan.
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Michele Markstein
2Biology Department, University of Massachusetts Amherst, 611 North Pleasant Street, Amherst MA 01003
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  • For correspondence: mmarkstein@bio.umass.edu
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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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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 04, 2019.
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ABC transporters confer multidrug resistance to Drosophila intestinal stem cells
Hannah Dayton, Jonathan DiRusso, Kristopher Kolbert, Olivia Williamson, Aiste Balciunaite, Edridge D’Souza, Kelly Becker, Elizaveta Hosage, Muneera Issa, Victoria Liu, Raghuvir Viswanatha, Shu Kondo, Michele Markstein
bioRxiv 511584; doi: https://doi.org/10.1101/511584
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ABC transporters confer multidrug resistance to Drosophila intestinal stem cells
Hannah Dayton, Jonathan DiRusso, Kristopher Kolbert, Olivia Williamson, Aiste Balciunaite, Edridge D’Souza, Kelly Becker, Elizaveta Hosage, Muneera Issa, Victoria Liu, Raghuvir Viswanatha, Shu Kondo, Michele Markstein
bioRxiv 511584; doi: https://doi.org/10.1101/511584

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