Drosophila AHR limits tumor growth and epithelial regeneration in the intestine
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ABSTRACT: The aryl hydrocarbon receptor (AHR) plays important roles in intestinal homeostasis, limiting tumour growth and promoting epithelial differentiation in the intestinal epithelium. Spineless, the Drosophila homolog of AHR, has only been studied in the context of development but not in the adult intestine. Here, we show that spineless is upregulated in the adult intestinal epithelium after infection with Pseudomonas entomophila (P.e.). Spineless knockdown increased stem cell proliferation following infection-induced injury but had no effect on fly survival. Spineless overexpression limited intestinal stem cell proliferation and reduced survival after infection. Limiting stem cell growth by Spineless proved beneficial in two tumour models, using either Notch RNAi or constitutively active Yorkie. Spineless overexpression suppressed tumour growth and approximately doubled the median survival. Spineless knockdown accelerated fly death following tumour induction. This was even more pronounced when flies were infected with a low dose of P. e. for the first day of tumour induction. RNA sequencing demonstrated that spineless was able to reverse a large proportion of the gene expression changes induced by constitutively active yorkie tumours. These findings demonstrate a new role for Spineless in the adult Drosophila midgut and emphasize the evolutionary conserved functions of AHR/Spineless in the regeneration of intestinal epithelium.
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE229388 | GEO | 2024/12/27
REPOSITORIES: GEO
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