Lucy O'Brien, Postdoctoral Faculty Sponsor
Basal stem cell progeny establish their apical surface in a junctional niche during turnover of an adult barrier epithelium.
Nature cell biology
Barrier epithelial organs face the constant challenge of sealing the interior body from the external environment while simultaneously replacing the cells that contact this environment. New replacement cells-the progeny of basal stem cells-are born without barrier-forming structures such as a specialized apical membrane and occluding junctions. Here, we investigate how new progeny acquire barrier structures as they integrate into the intestinal epithelium of adult Drosophila. We find they gestate their future apical membrane in a sublumenal niche created by a transitional occluding junction that envelops the differentiating cell and enables it to form a deep, microvilli-lined apical pit. The transitional junction seals the pit from the intestinal lumen until differentiation-driven, basal-to-apical remodelling of the niche opens the pit and integrates the now-mature cell into the barrier. By coordinating junctional remodelling with terminal differentiation, stem cell progeny integrate into a functional, adult epithelium without jeopardizing barrier integrity.
View details for DOI 10.1038/s41556-023-01116-w
View details for PubMedID 36997641
View details for PubMedCentralID 5742542
Fly Cell Atlas: A single-nucleus transcriptomic atlas of the adult fruit fly.
Science (New York, N.Y.)
2022; 375 (6584): eabk2432
For more than 100 years, the fruit fly Drosophila melanogaster has been one of the most studied model organisms. Here, we present a single-cell atlas of the adult fly, Tabula Drosophilae, that includes 580,000 nuclei from 15 individually dissected sexed tissues as well as the entire head and body, annotated to >250 distinct cell types. We provide an in-depth analysis of cell type-related gene signatures and transcription factor markers, as well as sexual dimorphism, across the whole animal. Analysis of common cell types between tissues, such as blood and muscle cells, reveals rare cell types and tissue-specific subtypes. This atlas provides a valuable resource for the Drosophila community and serves as a reference to study genetic perturbations and disease models at single-cell resolution.
View details for DOI 10.1126/science.abk2432
View details for PubMedID 35239393
A glucose-supplemented diet enhances gut barrier integrity in Drosophila.
Dietary intervention has received considerable attention as an approach to extend lifespan and improve aging. However, questions remain regarding optimal dietary regimes and underlying mechanisms of lifespan extension. Here, we asked how an increase of glucose in a chemically defined diet extends the lifespan of adult Drosophila We showed that glucose-dependent lifespan extension is not a result of diminished caloric intake, or changes to systemic insulin activity, two commonly studied mechanisms of lifespan extension. Instead, we found that flies raised on glucose-supplemented food increased the expression of cell adhesion genes, delaying age-dependent loss of intestinal barrier integrity. Furthermore, we showed that chemical disruption of the gut barrier negated the lifespan extension associated with glucose-treatment, suggesting that glucose-supplemented food prolongs adult viability by enhancing the intestinal barrier. We believe our data contribute to understanding intestinal homeostasis, and may assist efforts to develop preventative measures that limit effects of aging on health.
View details for DOI 10.1242/bio.056515
View details for PubMedID 33579694