Probing Plasmodium falciparum sexual commitment at the single-cell level

Abstract

Malaria parasites go through major transitions during their Background: complex life cycle, yet the underlying differentiation pathways remain obscure. Here we apply single cell transcriptomics to unravel the program inducing sexual differentiation in . Parasites have to make this Plasmodium falciparum essential life-cycle decision in preparation for human-to-mosquito transmission.By combining transcriptional profiling with quantitative imaging and Methods: genetics, we defined a transcriptional signature in sexually committed cells.We found this transcriptional signature to be distinct from general Results: changes in parasite metabolism that can be observed in response to commitment-inducing conditions. This proof-of-concept study provides a template to capture Conclusions: transcriptional diversity in parasite populations containing complex mixtures of different life-cycle stages and developmental programs, with important implications for our understanding of parasite biology and the ongoing malaria elimination campaign.

A single-cell atlas of Plasmodium falciparum transmission through the mosquito

“…Single-cell RNA sequencing (scRNA-seq) has transformed our ability to resolve cell-level heterogeneity in complex cell populations. Recent scRNA-seq views across the full life cycle of Plasmodium parasites, the etiological agents of malaria, have captured fine-scale developmental transitions driving progression through the life cycle at high resolution [5][6][7][8][9] . The Malaria Cell Atlas 6,8 was established as a data resource and website to provide an accessible route for scientists to explore patterns of gene expression in individual parasites across multiple developmental stages and parasite species.…”

Epigenetic Regulation and Chromatin Remodeling in Malaria Parasites

“…scRNA-seq was applied to different morphological stages of P. falciparum, including asexual (85,102), sexual (85,93,127), and mosquito (83,101) stages (Figure 1). These studies have, among other things, assessed the sex-specific markers of gametocytes (102,127) and described transcriptional signatures among committed and sexual stages (13,85,93). Moreover, additional regulators involved in sexual commitment were identified, such as transcription factors (TFs), SNF2 helicases, and histone-modifying enzymes (93).…”

Malaria parasites do respond to heat

“…While the nutrient sensor of this pathway was identified, the transcription factor(s) driving the gene expression changes were not [36]. The second example is the transcriptional response of P. falciparum to depletion of the serum lipid lysophosphatidylcholine (LysoPC), needed for phosphatidylcholine (PC) synthesis [37][38][39]. Depletion of LysoPC and downstream metabolites (e.g., choline) results in increased expression of genes encoding metabolic enzymes such as ethanolamine kinase (ek) and phosphoethanolamine Nmethyltransferase (pmt) that enable PC synthesis by an alternative pathway.…”

“…Additionally, LysoPC depletion results in increased sexual conversion [38], which is mediated by activation of the expression of the transcription factor pfap2-g [40] and its upstream regulator gdv1 [41] in only a subset of cells [37,38]. The sensor of LysoPC levels and the transcription factor(s) driving the compensatory metabolic response have not been identified.…”