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 ge...刚地弓形虫（Toxoplasma gondii）是一种原生动物寄生虫，其复杂且尚不完全明晰的发育过程对在中间宿主体内建立慢性感染至关重要。本研究针对5400余个处于速殖子（tachyzoite）和缓殖子（bradyzoite）阶段的弓形虫样本，采用三种经典研究菌株开展单细胞RNA测序（single-cell RNA-sequencing, scRNA-seq），构建了涵盖细胞周期与无性发育过程的综合转录组图谱，揭示了与各发育阶段相关的未知细胞状态及转录因子。 对SAG1相关序列（SAG1-related sequence, SRS）抗原库的分析显示，其呈现高度异质性且散发性的表达模式，该模式无法通过测序噪声、细胞周期或无性发育过程解释。 此外，本研究鉴定出AP2 IX-1作为转录因子，可调控从普遍表达的SAG1到此前未在速殖子中观测到的稀有表面抗原的转换。 另外，对弓形虫与疟原虫（Plasmodium）单细胞RNA测序结果的比较分析显示，基因的协同表达……