Characterizing sexual development of the human parasite Schistosoma mansoni

血吸虫病是一种被忽视的热带疾病，由寄生扁虫引起，称为寄生虫， 影响着世界上数亿最贫穷的人。这种疾病的病理学根源在于 事实上，寄生虫每天可以产下数百至数千个卵， 人类宿主的血管因此，了解控制 大量的鸡蛋生产可以提供新的机会，既可以限制疾病的传播， 并消除寄生虫引起的病理。有趣的是，雌性的雌虫只会 性成熟时，他们在不断的身体接触与男性蠕虫。事实上，女性 在没有雄虫的情况下生长，不会产生卵，也不会造成严重的不良后果。 在他们的主人。虽然雄虫对雌虫性发育的要求是 描述了近100年前，很少有人了解这一过程是如何调节的， 分子水平。解决这一问题的一个主要障碍是，目前的文化条件不 在体外支持性发育。为了解决这个问题，我们开发了一种新的 支持雄性诱导的雌性性发育和长期产卵的培养基制剂 体外生产。利用这一媒介，我们提出了两个重要的意见。一是 发现雌虫在与雄虫配对后立即发生基因表达变化， 发生在生殖器官，而是在寄生虫的体细胞组织，包括神经元和 肌肉细胞其次，我们鉴定了一种在神经系统中高度表达的转录因子， 雌虫与雄虫配对后，对雌虫性发育至关重要的肌肉细胞。基于 根据这些数据，我们假设雌虫的体细胞非生殖细胞类型是 负责感知雄虫的存在，并反过来调节 生殖器官。定义直接负责感知存在的细胞类型 雄虫可以提供重要的线索， 女性性发育因此，我们将在两个具体目标中检验我们的中心假设。在 具体目标1我们将描述生殖和体细胞的细胞和分子反应， 利用基本的发育生物学， 方法和单细胞RNA测序。Specific Aim 2将利用RNA干扰和单一 细胞RNA测序，以发现基因和体细胞类型，是必不可少的控制女性 成熟，并确定这些基因如何协调一致，以协调女性的反应， 和一只雄性配对我们希望这些研究能够确定刺激女性的信号事件， 成熟，并希望他们将提出新的治疗靶点，对crossome。

Schistosomiasis is a neglected tropical disease caused by parasitic flatworms, called schistosomes, that affects hundreds of millions of the world’s poorest people. The pathology of this disease stems from the fact that schistosomes can lay hundreds-to-thousands of eggs per day while living in the blood vessels of their human hosts. Therefore, understanding the mechanisms that control schistosome egg production could present new opportunities to both limit the spread of the disease and abrogate the pathology caused by the parasite. Interestingly, female schistosomes only become sexually mature when they are in constant physical contact with a male worm. Indeed, females grown in the absence of male worms produce no eggs and cause no serious adverse consequences in their hosts. Although the requirement of male worms for female sexual development was described almost 100 years ago, there are few insights into how this process is regulated on a molecular level. A major impediment for addressing this issue is that current culture conditions do not support schistosome sexual development in vitro. To address this issue we have developed a novel media formulation that supports male-induced female sexual development and long-term egg production in vitro. Capitalizing on this medium, we have made two important observations. First, we find that gene expression changes in females immediately upon pairing with a male worm do not occur in the reproductive organs, but rather in the parasite’s somatic tissues including neurons and muscle cells. Second, we identified a transcription factor highly expressed in the nervous system and muscle cells that is essential for female sexual development after pairing with a male worm. Based on these data, we hypothesize that somatic non-reproductive cell types in the female worm are responsible for perceiving the presence of the male worm and in turn regulating the development of the reproductive organs. Defining the cell types directly responsible for perceiving the presence of the male worm could provide important clues about the nature of the male-derived signal that controls female sexual development. Therefore, we will test our central hypothesis in two specific aims. In Specific Aim 1 we will describe the cellular and molecular response of the reproductive and somatic tissues of the female worm to pairing with a male worm using basic developmental biology approaches and single cell RNA sequencing. Specific Aim 2 will utilize RNA interference and single cell RNA sequencing to discover genes and somatic cell types that are essential for controlling female maturation and determine how these genes act in concert to coordinate the female response to pairing with a male. We expect these studies to define the signaling events that stimulate female maturation and hope they will suggest new therapeutic targets against schistosomes.