A single-parasite transcriptional atlas of Toxoplasma Gondii reveals novel control of antigen expression.
Yuan XueTerence C TheisenSuchita RastogiAbel FerrelStephen R QuakeJohn C BoothroydPublished in: eLife (2020)
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 AP2IX-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.
Keyphrases
- single cell
- toxoplasma gondii
- cell cycle
- rna seq
- transcription factor
- poor prognosis
- cell proliferation
- plasmodium falciparum
- high throughput
- gene expression
- binding protein
- long non coding rna
- genome wide
- machine learning
- stem cells
- air pollution
- dendritic cells
- immune response
- genome wide identification
- dna methylation
- copy number
- oxidative stress
- cell therapy
- drug induced
- life cycle
- heat stress