美国怀特黑德生物医学研究所Sebastian Lourido团队鉴定出一个弓形虫分化的关键调节因子。2020年1月16日，《细胞》在线发表了这一研究成果。

通过Cas9介导的筛选和单细胞分析，研究人员确定了在细胞培养和小鼠感染中弓形虫分化所必需的Myb样转录因子（BFD1）。BFD1在压力下积累，其合成表达足以驱动分化。与它作为转录因子的功能一致，BFD1结合了许多阶段特异性基因的启动子，并代表了ApiAP2因子的对立点，而ApiAP2因子主导了人们目前对寄生虫基因调控的观点。BFD1提供了一种遗传开关来研究和控制弓形虫的分化，并将为预防和治疗慢性感染提供信息。

据了解，弓形虫长期感染世界四分之一的人口，其复发会导致免疫功能低下的人危及生命，并导致免疫功能正常的眼部病变。急性期速殖子分化成慢性期缓殖子，它们形成对免疫清除和现有疗法有抵抗力的细胞内囊肿。尽管是由培养中的压力有效触发的，但这种分化的分子基础仍是未知的。

附：英文原文

Title: Identification of a Master Regulator of Differentiation in Toxoplasma

Author: Benjamin S. Waldman, Dominic Schwarz, Marc H. Wadsworth, Jeroen P. Saeij, Alex K. Shalek, Sebastian Lourido

Issue&Volume: January 16, 2020

Abstract: Toxoplasma gondii chronically infects a quarter of the world’s population, and its recrudescence can cause life-threatening disease in immunocompromised individuals and recurrent ocular lesions in the immunocompetent. Acute-stage tachyzoites differentiate into chronic-stage bradyzoites, which form intracellular cysts resistant to immune clearance and existing therapies. The molecular basis of this differentiation is unknown, despite being efficiently triggered by stresses in culture. Through Cas9-mediated screening and single-cell profiling, we identify a Myb-like transcription factor (BFD1) necessary for differentiation in cell culture and in mice. BFD1 accumulates during stress and its synthetic expression is sufficient to drive differentiation. Consistent with its function as a transcription factor, BFD1 binds the promoters of many stage-specific genes and represents a counterpoint to the ApiAP2 factors that dominate our current view of parasite gene regulation. BFD1 provides a genetic switch to study and control Toxoplasma differentiation and will inform prevention and treatment of chronic infections.

DOI: 10.1016/j.cell.2019.12.013

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31375-3