A cell atlas of the adult female Aedes aegypti midgut revealed by single-cell RNA sequencing

The mosquito midgut functions as a key interface between pathogen and vector. However, studies of midgut physiology and associated virus infection dynamics are scarce, and inCulex tarsalis- an extremely efficient vector of West Nile virus (WNV) - nonexistent. We performed single-cell RNA sequencing onCx. tarsalismidguts, defined multiple cell types, and determined whether specific cell types are more permissive to WNV infection. We identified 20 cell states comprised of 8 distinct cell types, consistent with existing descriptions ofDrosophilaandAedes aegyptimidgut physiology. Most midgut cell populations were permissive to WNV infection. However, there were higher levels of WNV RNA (vRNA) in enteroendocrine cells and cells enriched for mitochondrial genes, suggesting enhanced replication in these populations. In contrast, proliferating intestinal stem cell (ISC) populations had the lowest levels of vRNA, a finding consistent with studies suggesting ISC proliferation in the midgut is involved in viral control. Notably, we did not detect significant WNV-infection induced upregulation of canonical mosquito antiviral immune genes (e.g., AGO2, R2D2, etc.) at the whole-midgut level. Rather, we observed a significant positive correlation between immune gene expression levels and vRNA in individual cells, suggesting that within midgut cells, high levels of vRNA may trigger antiviral responses. Our findings establish aCx. tarsalismidgut cell atlas, and provide insight into midgut infection dynamics of WNV by characterizing cell-type specific enhancement/restriction of, and immune response to, infection at the single-cell level.

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Single-cell transcriptional landscapes ofAedes aegyptimidgut and fat body after a bloodmeal

Vial,

Lopez-Maestre,

Couderc

et al. 2024

Preprint

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Aedes aegypti mosquitoes are vectors for numerous arboviruses that have an increasingly substantial global health burden. Following a bloodmeal, mosquitoes experience significant physiological changes, primarily orchestrated by the midgut and fat body tissues. These changes begin with digestion and culminate in egg production. However, our understanding of those key processes at the cellular and molecular level remains limited. We have created a comprehensive cell atlas of the mosquito midgut and fat body by employing single-cell RNA sequencing and metabolomics techniques. This atlas unveils the dynamic cellular composition and metabolic adaptations that occur following a bloodmeal. Our analyses reveal highly diverse cell populations, specialized in digestion, metabolism, immunity, and reproduction. While the midgut primarily comprises enterocytes, enteroendocrine and intestinal stem cells, the fat body consists not only of trophocytes and oenocytes, but also harbors a substantial hemocyte population and a newly found fat body-yolk cell population. The fat body exhibits a complex cellular and metabolomic profile and exerts a central role in coordinating immune and metabolic processes. Additionally, an insect-specific virus, PCLV (Phasi Charoen-Like Virus) was detected in single cells, mainly in the midgut a week after the bloodmeal. These findings highlight the complexity of the mosquito abdominal tissues, and pave the way towards the development of exquisitely refined vector control strategies consisting of genetically targeting specific cell populations and metabolic pathways necessary for egg development after a bloodmeal.

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A cell atlas of the adult female Aedes aegypti midgut revealed by single-cell RNA sequencing

Cited by 3 publications

References 30 publications

Deciphering cellular heterogeneity in Spodoptera frugiperda midgut cell line through single cell RNA sequencing

Deciphering cellular heterogeneity in Spodoptera frugiperda midgut cell line through single cell RNA sequencing

A single-cell atlas of theCulex tarsalismidgut during West Nile virus infection

Single-cell transcriptional landscapes ofAedes aegyptimidgut and fat body after a bloodmeal

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