ETS-guided iPSC-endothelial models recapitulate malaria pathogenesis
Korbmacher, F.; Fleckenstein, H.; Long, R. K. M.; Polinski, P.; Piatti, L.; Lopez Gutierrez, B.; Batzilla, A.; Crusius, D.; Trivedi, V.; Ebisuya, M.; Bernabeu, M.
Show abstract
The sequestration of the malaria parasite Plasmodium falciparum in the microvasculature is a major driver of severe malaria, but its pathogenic mechanisms still remain unknown. Advancements in induced pluripotent stem cell (iPSC) technologies offer unique opportunities to study parasite interactions with blood vessels in a well-defined host environment. However, endothelial iPSC-differentiation methods often result in cells with mixed epithelial identity. Here, we have generated an iPSC line with inducible and simultaneous expression of ETS transcription factors (ETV2, FLI1, ERG), which resulted in improved endothelial cell identity and strong barrier function. These cells display a high affinity to infected red blood cells. Exposure to parasite products caused significant endothelial metabolic changes and splicing alterations. Furthermore, it disrupted the iPSC-endothelial barrier, as a consequence of transcriptional downregulation of key barrier processes, and alteration of severe malaria biomarkers. Our novel iPSC-based approach represents a new in vitro platform to study the pathogenesis of vascular infections.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Total parasite biomass but not peripheral parasitaemia is associated with endothelial and haematological perturbations in Plasmodium vivax patients 95%
- UFMTrack: Under-Flow Migration Tracker enabling analysis of the entire multi-step immune cell extravasation cascade across the blood-brain barrier in microfluidic devices 93%
- Mycolactone causes destructive Sec61-dependent loss of the endothelial glycocalyx and vessel basement membrane: a new indirect mechanism driving tissue necrosis in Mycobacterium ulcerans infection 93%
Similar papers in this journal
- Innate immune cell response to host-parasite interaction in a human intestinal tissue microphysiological system 93%
- Granuloma Dual RNA-Seq Reveals Composite Transcriptional Programs Driven by Neutrophils and Necrosis within Tuberculous Granulomas 93%
- Immune engineered extracellular vesicles to modulate T cell activation in the context of type 1 diabetes 93%
Similar papers in this journal
- Endothelial exosome plays functional role during rickettsial infection 94%
- Systemic host inflammation induces stage-specific transcriptomic modification and slower maturation in malaria parasites 94%
- The Plasmodium falciparum protein VCAP1 controls Maurer’s cleft morphology, knob architecture and PfEMP1 trafficking 94%
Similar papers in this journal
- Biomechanical interactions of Schistosoma mansoni eggs with vascular endothelial cells facilitate egg extravasation 92%
- Differential contribution of two organelles of endosymbiotic origin to iron-sulfur cluster synthesis and overall fitness in Toxoplasma 92%
- The malaria parasite PP1 phosphatase controls the initiation of the egress pathway of asexual blood-stages by regulating the rounding-up of the vacuole 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.