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Single-cell atlases of Aedes aegypti midgut and fat body reveal cellular and metabolic dynamics after a blood-meal

ABSTRACT: Aedes aegypti mosquito, vector for several viral diseases, undergoes significant physiological changes after a blood meal. Through single-cell RNA sequencing and metabolomics, we unveiled dynamic cellular composition and metabolic adaptations within abdominal midgut and fat body tissues. We revealed high cell diversity, specialized in digestion, metabolism, immunity, and reproduction. While the midgut primarily comprises enterocytes, enteroendocrine, cardia and intestinal stem cells, the fat body consists of not only trophocytes and oenocytes, but also a substantial population of hemocytes and fat body-yolk cells (FYC). The fat body, exhibiting a more complex metabolomic profile than the midgut, played a central role in immune and metabolic gene expression, particularly within trophocytes and FYCs. Additionally, insect-specific viruses were detected at the single-cell level, mainly in the midgut at later stages post-blood meal. These findings offer new vector control strategies by targeting specific abdominal cell populations and metabolic pathways involved after a blood meal.

ORGANISM(S): Aedes aegypti

PROVIDER: GSE281673 | GEO | 2024/11/17

REPOSITORIES: GEO

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Project description:Mosquitoes possess an innate immune system that is capable of limiting infection by a variety of pathogens, including the Plasmodium spp. parasites responsible for human malaria. The Anopheles immune deficiency (IMD) innate immune signaling pathway confers resistance to Plasmodium falciparum. While some previously identified Anopheles anti-Plasmodium effectors are regulated through signaling by Rel2, the transcription factor of the IMD pathway, many components of this defense system remain uncharacterized. To begin to better understand the regulation of immune effector proteins by the IMD pathway, we used oligonucleotide microarrays and iTRAQ to analyze differences in mRNA and protein expression, respectively, between transgenic An. stephensi mosquitoes exhibiting blood meal-inducible overexpression of an active recombinant Rel2 and their wild-type conspecifics. Numerous genes were differentially regulated at both the mRNA and protein levels following induction of Rel2. While multiple immune genes were up-regulated, a majority of the differentially expressed genes have no known immune function in mosquitoes. Identified sequences were assigned putative functions and gene ontology (GO) terms based on homology to previously annotated A. gambiae gene sequences. Selected up-regulated genes from multiple GO categories were tested for both anti-Plasmodium and anti-bacterial action using RNA interference (RNAi). Based on our experimental findings, we conclude that increased expression of the IMD immune pathway-controlled transcription factor Rel2 affects the expression of numerous genes with diverse functions, suggesting a broader physiological impact of immune activation and possible functional versatility of Rel2. Our study has identified multiple novel anti-Plasmodium effectors. Midguts from midgut-specific transgenic A. stephensi at 6 and 12 hours post-blood meal and fat bodies from fat body-specific transgenic A. stephensi at 12 and 18 hours post-blood meal were compared to wild-type A. stephensi at the same time points. 3 biological replicates and 1 pseudo-replicate per array.

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Single-cell atlases of Aedes aegypti midgut and fat body reveal cellular and metabolic dynamics after a blood-meal

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