A single cell atlas of sexual development in Plasmodium falciparum

Abstract The developmental decision made by malaria parasites to become sexual underlies all malaria transmission. Here, we describe a rich atlas of short and long-read single-cell transcriptomes of over 37,000 Plasmodium falciparum cells across intraerythrocytic asexual and sexual development. We used the atlas to explore transcriptional modules and exon usage along sexual development, and expanded it to include malaria parasites collected from a Malian individual naturally infected with multiple P. falciparum strains. We investigated genotypic and transcriptional heterogeneity within and among these wild strains at a single-cell level for the first time, finding considerable differential expression between different strains even within the same host. This work is a key addition to the Malaria Cell Atlas, enabling a deeper understanding of the biology and diversity of transmission stages. One sentence summary This addition to the Malaria Cell Atlas presents an analysis of sexual development and uses it to explore a natural infection.