The Malaria Cell Atlas: a comprehensive reference of single parasite transcriptomes across the complete Plasmodium life cycle

Abstract

One Sentence Summary. Single-cell transcriptomics of malaria parasites illuminates gene usage across the entire life cycle, and allows precise developmental time assignment of parasite cells from distantly related Plasmodium species. AbstractMalaria parasites adopt a remarkable variety of morphological life stages as they transition through multiple mammalian host and mosquito vector environments. Here we profile the single-cell transcriptomes of thousands of individual parasites, deriving the first high-resolution transcriptional atlas of the entire Plasmodium berghei life cycle. We then use our atlas to precisely define developmental stages of single cells from three different human malaria parasite species, including parasites isolated directly from infected individuals. The Malaria Cell Atlas provides both a comprehensive view of gene usage in a complex eukaryotic parasite and an open access reference data set for the study of malaria parasites.

A Natural Peptide Antigen within the Plasmodium Ribosomal Protein RPL6 Confers Liver TRM Cell-Mediated Immunity against Malaria in Mice

“…TRAP is highly expressed by sporozoites, but not by liver-stage parasites (Amino et al, 2006), which may limit the amount of antigen that infected hepatocytes can display throughout liver-stage development for recognition by liver T RM cells. By contrast, significant expression of the RPL6 gene has been shown throughout the liver-stage and during the blood stage of P. yoelii and P. berghei infection (Hall et al, 2005;Howick et al, 2019;Sacci et al, 2005;Tarun et al, 2008;Zhou rAAV-NVF and were challenged 99 days later with 200 P. berghei sporozoites. (I) Sterile protection by endogenous PbRPL6 120-127 -specific liver T RM cells generated after delayed trapping using prime-and-trap vaccination targeting RPL6.…”

“…Significant protection in the absence of rAAV indicated that PbRPL6 120-127 was an excellent antigen for vaccination against liver-stage malaria. Although we showed above that NCY was not the cognate antigen of PbT-I cells (Figures 3A and S3C), this epitope is derived from a natural Plasmodium protein (Howick et al, 2019) and can be recognized by PbT-I cells (Lau et al, 2014). Thus, we sought to define its protective potential.…”

Using single-cell transcriptomics to understand functional states and interactions in microbial eukaryotes

“…For example, cell stage-specific transcriptomes for protists with complex life cycles allowed the dissection of gene expression phenotypes associated with cell growth (e.g. in the diatom Thalassiosira pseudonana [67]) and with temporal cell types in organisms like the ichthyosporean Creolimax fragrantissima [68], the choanoflagellate Salpingoeca rosetta, the amoebozoans Dictyostelium discoideum and Dictyostelium purpureum [69], the apicomplexan Plasmodium falciparum [70,71] or the filasterean Capsaspora owczarzaki [30]. Furthermore, genome-wide chromatin profiling experiments in some of these species defined the regulatory genome dynamics underlying temporal cell differentiation [72][73][74].…”

Evaluation of DNA extraction methods on individual helminth egg and larval stages for whole genome sequencing

“…Such approaches have begun to be used on parasitic species such as Plasmodium spp . (Howick et al, 2019;Ngara et al, 2018;Reid et al, 2018;Trevino et al, 2017) , but are yet to be adopted by helminth parasitologists. Although these low-input, high-throughput approaches are not designed -and perhaps not currently suitable -for diagnostic applications, the developments in molecular biology techniques for low input sequencing can benefit the use of genomics for helminth applications.…”