First Advisor

Judith Leatherman

First Committee Member

James Haughian

Second Committee Member

Nicholas Pullen

Degree Name

Master of Science

Document Type

Thesis

Date Created

5-7-2024

Abstract

In chemotherapy treatments most tumor cells are destroyed by drugs, but some tumor cells are drug resistant, and these are known as cancer stem cells (CSCs). Normal adult stem cells are also chemo resistant. Therefore, investigation of normal stem cells can be useful to provide further knowledge of CSCs. One of the primary ways that CSCs achieve drug resistance is by drug efflux through transmembrane pumps called ATP-binding cassette (ABC) transporters. Many studies on ABC transporters have been performed in vitro using cultured cell lines, but very few studies have been performed on normal stem cell populations in vivo. Drosophila is widely used as a model organism and the germline testis stem cell niche is well characterized and can be easily genetically manipulated. The testis niche has two stem cell populations—the germline stem cells (GSCs) and cyst stem cells (CySC). To investigate drug efflux in the normal condition in this niche I incubated unfixed testes in the autofluorescent chemotherapy drugs Doxorubicin and Topotecan. We found that drug intensity was significantly higher in differentiating germline daughter cells than in GSCs, but there was no significant difference between CySCs and their differentiating daughters. We also measured the drug intensity between GSC and spermatogonia in a stressed condition and we found that most of the stressed GSCs and spermatogonia showed less drug accumulation compared with control testes. Inhibition of several different ABC transporter genes caused the drug intensity difference to be lost, suggesting that GSCs may efflux more drug than their differentiating daughter cell.

Abstract Format

html

Disciplines

Developmental Biology

Extent

83 pages

Rights Statement

Copyright is held by the author

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