Single-cell transcriptomics reveals transcriptional programs underlying male and female cell fate during Plasmodium falciparum gametocytogenesis

• The Apicomplexa constitute a large phylum of parasitic protozoa with complex life cycles that typically include meiotic sex. The life cycle of the malaria parasite, Plasmodium falciparum, includes obligate transition and stage development between a human and mosquito host. Asexual parasite replication in the human erythrocytes is followed by differentiation which leads to the formation of a precursor gamete stage, referred to as gametocytes. The gametocyte stage is solely responsible for malaria transmission into the mosquito vector where gamete fusion followed by meiosis occurs. How the parasite differentiates into male and female gametocytes in the absence of sex chromosomes largely remains an open question. Here we combine FACS-based cell enrichment of a gametocyte reporter line followed by single-cell RNA-seq, to enable targeted characterization of the entire gametocyte developmental stage. Our data defines differential transcriptional programs during male and female gametocyte development and highlights a bifurcation point for sexual cell fate. We perform prediction analyses of novel candidate driver genes underlying P. falciparum male and female lineage development. Our data indicate that a large panel of genes linked to the inner membrane complex, known to be involved in morphological life cycle changes, appears to be uniquely expressed in the female gametocyte lineage. Additionally, we delineate the timing of expression of members of the ApiAP2 family of transcription factors and predict their specificity in male and female P. falciparum gametocyte development. A motif-driven gene regulatory network analysis indicates a major role for AP2-G5 in downstream gene regulation along the male lineage developmental trajectory. In total, we anticipate that this study provides the malaria community with an important resource for the development of transmission-blocking intervention strategies.

Subject headings

NATURVETENSKAP  -- Biologi -- Cellbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Cell Biology (hsv//eng)

NATURVETENSKAP  -- Biologi -- Mikrobiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Microbiology (hsv//eng)

NATURVETENSKAP  -- Biologi -- Bioinformatik och systembiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)

Keyword

Plasmodium falciparum

transmission

development

sex determination

molekylär biovetenskap

Molecular Bioscience

Publication and Content Type

vet (subject category)

ovr (subject category)