ABC transporters support Drosophila intestinal stem and progenitor cells during cytotoxic challenge
- 1Harvard Medical School
Abstract
Adult stem cells can survive diverse insults, from ionizing radiation to toxic chemicals. In vertebrates, ABC transporter expression and dye-efflux capacity have been associated with stem-cell protection and multidrug resistance. How compound accumulation differs between adult stem cells and their differentiated daughters within an intact tissue remains poorly understood. Here, we show that adult Drosophila intestinal stem/progenitor cells maintain a distinct low-accumulation state for membrane-permeable compounds and that ABC transporters contribute to this phenotype and to the response to cytotoxic stress. Across nine membrane-permeable probes, stem/progenitor cells accumulated eight at lower levels than differentiated enterocytes. We selected tetramethylrhodamine methyl ester (TMRM), a membrane-permeable fluorescent probe that showed a strong difference in accumulation between stem/progenitor cells and enterocytes, as a quantitative readout for an RNAi screen of all 56 Drosophila ABC-family genes. The screen identified seven candidate transporters whose depletion increased the stem/progenitor-to-enterocyte TMRM fluorescence ratio. Further characterization of one of them, ABCB7, showed that ABCB7-depleted guts contained fewer mitotic cells during cytotoxic drug exposure. These results implicate ABC transporters in lower compound accumulation in Drosophila intestinal stem/progenitor cells and support a role for ABC transporters in their response to cytotoxic challenge.
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BibTeX
@misc{dayton2026transporters,
title = {{ABC transporters support Drosophila intestinal stem and progenitor cells during cytotoxic challenge}},
author = {H. Dayton and J. Russo and K. E. Kolbert and O. Williamson and A. Balciunaite and E. DSouza and K. Becker and E. Hosage and M. Issa and V. Lu and R. Viswanatha and S. Kondo and N. Perrimon and M. M. Markstein},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.05.756803},
url = {https://www.biorxiv.org/content/10.64898/2026.10.05.756803v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - ABC transporters support Drosophila intestinal stem and progenitor cells during cytotoxic challenge
AU - H. Dayton
AU - J. Russo
AU - K. E. Kolbert
AU - O. Williamson
AU - A. Balciunaite
AU - E. DSouza
AU - K. Becker
AU - E. Hosage
AU - M. Issa
AU - V. Lu
AU - R. Viswanatha
AU - S. Kondo
AU - N. Perrimon
AU - M. M. Markstein
PY - 2026
DA - 2026/10/05
PB - bioRxiv
DO - 10.64898/2026.10.05.756803
UR - https://www.biorxiv.org/content/10.64898/2026.10.05.756803v1
AB - Adult stem cells can survive diverse insults, from ionizing radiation to toxic chemicals. In vertebrates, ABC transporter expression and dye-efflux capacity have been associated with stem-cell protection and multidrug resistance. How compound accumulation differs between adult stem cells and their differentiated daughters within an intact tissue remains poorly understood. Here, we show that adult Drosophila intestinal stem/progenitor cells maintain a distinct low-accumulation state for membrane-permeable compounds and that ABC transporters contribute to this phenotype and to the response to cytotoxic stress. Across nine membrane-permeable probes, stem/progenitor cells accumulated eight at lower levels than differentiated enterocytes. We selected tetramethylrhodamine methyl ester (TMRM), a membrane-permeable fluorescent probe that showed a strong difference in accumulation between stem/progenitor cells and enterocytes, as a quantitative readout for an RNAi screen of all 56 Drosophila ABC-family genes. The screen identified seven candidate transporters whose depletion increased the stem/progenitor-to-enterocyte TMRM fluorescence ratio. Further characterization of one of them, ABCB7, showed that ABCB7-depleted guts contained fewer mitotic cells during cytotoxic drug exposure. These results implicate ABC transporters in lower compound accumulation in Drosophila intestinal stem/progenitor cells and support a role for ABC transporters in their response to cytotoxic challenge.
ER -