A single-parasite transcriptional atlas of Toxoplasma gondii reveals novel control of antigen expression

Toxoplasma gondii, a protozoan parasite, undergoes a complex and poorly
understood developmental process that is critical for establishing a
chronic infection in its intermediate hosts. Here, we applied single-cell
RNA-sequencing (scRNA-seq) on >5,400 Toxoplasma in both tachyzoite
and bradyzoite stages using three widely studied strains to construct a
comprehensive atlas of cell-cycle and asexual development, revealing
hidden states and transcriptional factors associated with each
developmental stage. Analysis of SAG1-related sequence (SRS) antigenic
repertoire reveals a highly heterogeneous, sporadic expression pattern
unexplained by measurement noise, cell cycle, or asexual development.
Furthermore, we identified AP2 IX-1 as a transcription factor that
controls the switching from the ubiquitous SAG1 to rare surface antigens
not previously observed in tachyzoites. In addition, comparative analysis
between Toxoplasma and Plasmodium scRNA-seq results reveals concerted
expression of gene sets, despite fundamental differences in cell division.
Lastly, we built an interactive data-browser for visualization of our
atlas resource.